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Nanostructure Lipid Carrier (NLC): the new generation of lipid nanoparticles
... [4][5][6] NLC is a lipid nanoparticle generally consisting of solid lipids, liquid lipids, and emulsifiers having a particle size distribution of up to 500 nm. 7,8 The type and ratio of lipids used in NLC affect the morphology and particle size, trapping effectiveness, system stability, and penetration of active compounds into the skin. The combination of solid lipids and liquid lipids is known to affect the crystallinity index of the NLC matrix. ...
... Liquid lipids, plant oils, or fixed oils such as olive oil and VCO can be used. [6][7][8][9] The presence of plant oil liquid lipids in NLC can provide an emollient effect and increase occlusion by preventing water evaporation from the skin layer, resulting in increased skin hydration and increased penetration of active ingredients into the skin. 10 However, the presence of large amounts of plant oil causes a "greasy" feeling in use, so it is necessary to combine it with essential oils, for example, peppermint oil which also functions as an enhancer. ...
Background:
Coenzyme Q10 is formulated into Nanostructured Lipid Carrier (NLC) added with peppermint oil (PO) 0% (F1), 1% (F2), 1.5% (F3) and 2% (F4) to increase its penetration.
Objective:
This study aims to determine the effect of PO addition on the irritability, stability, and penetration of Coenzyme Q10 in the NLC.
Methods:
Coenzyme Q10 NLC was prepared using the High Shear Homogenization method. Furthermore, physical characterization was carried out. Physical stability testing was carried out for 90 days at a temperature of 25±5oC and an RH of 60±10%. The in vivo irritation test was observed for mice's back skin after 24 hours while the penetration study was further evaluated at 2 hours of the sample application.
Results:
Increasing the PO amount into Coenzyme Q10 NLC reduced the viscosity which was 329.1±15.5 cps for PO 0% to 219.9±2.9 cps for 2% addition. The observation of particle morphology showed that all NLC Coenzyme Q10 has a spherical particle shape with particle size between 188.25±13.22 to 197.80±14.19 nm. All formulas had high entrapment efficiency (>80%). PO addition did not cause changes in physical characteristics during 90 days of storage. The 24 hours' irritation test showed that F2 and F3 are non-irritating. By PO addition skin penetration improved at 2 hours' penetration study.
Conclusion:
PO addition up to 2% reduced viscosity, but did not affect particle size and morphology of Coenzyme Q10 NLC. Addition of PO up to 1.5% increased entrapment efficiency, did not irritate and increased the penetration of Coenzyme Q10 NLC.
... NLC also has many advantages over conventional drug delivery systems, such as creams, tinctures, lotions and emulsions. NLC has several advantages such as controlled drug release, negligible skin irritation, protection against active compounds and targeted drug delivery (Kaur, 2015) In this research, an anti-aging body lotion product was developed which contains CoQ10 in the NLC system. However, this product has no fragrance. ...
Lavender oil and lime oil contain linalool which has a relaxing effect. This oil has potential as a fragrance in antiaging body lotion products containing Coenzyme Q10 (CoQ10) in the Nanostructured Lipid Carriers System (NLC). This study aimed to analyzed the physical characteristics and consumer preference level for anti aging body lotion containing NLC-CoQ10. NLC-CoQ10 was prepared using the High Shear Homogenization method. For F1 (Formula 1), NLC-CoQ10 is mixed with a gel base and lavender oil. For F2 (Formula 2), the type of essential oil added is lime oil. These two forms when compared with F0 (Formula 0 = formula without essential oils). The physical properties observed included organoleptic, pH, homogeneity, spreadability, and viscosity. Organoleptic test and homogeneity were analyzed descriptively. While the pH, spreadability, and viscosity were analyzed using One Way Anova. In the preference level test, the aspect that is assessed is aroma. This test was analyzed statistically using the Univariate method. Based on the physical characteristic test, it is known that the three formulas have the same color, consistency, and homogeneity. The difference between the three formulas lies in their aroma. F0 is unscented; F1 has a lavender scent; F2 has a lime scent. The viscosity of the three formulas is also different but does not affect the spreadability value. Based on the aroma preference level test, it is known that F2 has the highest value. The type of essential oil affects the aroma and level of preference of the panelists. The most preferred formula is a formula containing lime oil. Keyword: Anti-aging; Body Lotion; Koenzim Q10; Lavender Oil; Lime Oil
... Imperfect crystal-type NLCs are achieved using glycerides composed of different fatty acids. Maximum imperfections (disordered crystal) accommodate more actives, resulting in high drug loading 41,42 . ...
Purpose: The present study was aimed at preparing stable dry adsorbed nanoparticles (DANs) of curcumin (CUR) and piperine (PIP) loaded nanostructured lipid carriers (NLCs).
Methods: CUR and PIP-loaded NLCs (CP NLCs) were prepared by modified hot-melt emulsification using precirol ATO5 (PRE) as solid lipid, labrafac lipophile WL1349 (LAF) as liquid lipid, and a combination of tween 80 (T80) with gelucire 50/13 (G50/13) as surfactants. The NLCs system was subjected to physical stability,
particle size, zeta potential, thermal behaviour, crystallinity study and in-vitro drug release. Further, an evaporative drying technique converted the NLC system into stable DANs by adsorbing onto mannitol (Pearlitol 200SD). The DANs were
characterized for redispersion properties, particle size, flow properties and in-vitro drug release. The stability studies were carried out for 30 days.
Results: The optimized CP NLCs were of imperfect type and had a mean particle size of 248.5 ± 12.8 nm (size distribution of 0.216 ± 0.021), a zeta potential of -9.03 ± 0.53 mV, an entrapment efficiency (EE) of 99.80 ± 0.21% (CUR), 100.05 ± 0.07% (PIP)
with a drug recovery of 99.70 ± 0.21% (CUR) and 100.36 ± 0.12% (PIP). The X-ray diffraction pattern and endothermic peaks confirmed the encapsulation of actives in lipid matrices. The in-vitro drug release showed controlled release for 24 h. The
optimized DANs led to maximum redispersion and retained a particle size of 268.4 ± 23.1 nm (distribution 0.235 ± 0.037) with controlled release similar to CP NLCs. The CP NLCs DANs showed reasonable stability for 30 days.
Conclusions: The developed CP NLCs DANs showed a controlled release profile, and the adsorption technique can be used to improve the stability of NLC dispersion. The DANs can be offered in patient-friendly dosage forms such as sachets, capsules, and compressed tablets.
... The formulation was optimized by design of experiment (CCD-RSM). [29,30] ...
The experimental work and design on the creation and enhanced of a quetiapine fumarate nanostructured lipid transport system for oral drug delivery of used for disease treatment of Schizophrenia. Because quetiapine fumarate is a substrate for Para-glycoprotein inhibitors organize on the surface of the gut and endothelial cells of the BBB. An inhibitor of curcumin is used as drug aid substance entrance to these cells. It was also planned to increase the drug's bioavailability, as it belongs to biopharmaceutical categorization system class II and has a low oral bioavailability of 9%, with a low dose so that the drug's negative effects could be avoided. Hot homogenization method was used to design nanostructured lipid transport systems from cholesterol and oleic acid prepared from different types of lipids one is solid lipid and liquid lipid, respectively. Various types of Surfactant are used in the formulation of nano structured lipid transport system that is vitamin E, tocopherol and polyethylene glycol succinate, which has frequent properties. The primary aim was to enhanced lipid concentration through various experimental design. The respondent were simultaneously charcterized using Deringer's desirability function, which yielded a desirability value of D 0.893, indicating a high degree of global optimisation. To evaluate quetiapine fumarate and curcumin in formulations, a simultaneous approach using RP-HPLC was devised. The configuration of nanostructured lipid transport were characterised for several physiochemical properties, as well as the influence of cholesterol and oleic acid on particle size and transparency. Ex vivo permeability tests were performed to examine the effect of curcumin when coupled with quetiapine fumarate.
... However, at a temperature below the melting point, this lipid mixture should be homogenous with no phase separation; in other words, oily liquid lipids should be present as nano-sized compartments within the solid crystalline matrix [4,5]. The various examples of lipids along with their applications in formulation development are summarized in Table 1 [6][7][8][9][10][11][12][13][14][15][16][17]. ...
Background
Lipid nanocarriers (NLCs) have undergone significant research over the past two decades to determine how well they target drugs to important parts of the human body, such as the central nervous system (CNS), the heart region, tumor cells, etc.
Objective
The objective of this review paper was to review and critically summarize recent progress in NLC for targeting CNS.
Method
The structure, classification, elements, and numerous preparation techniques have been carefully outlined in this paper, along with their benefits and drawbacks, as demonstrated by several research investigations.
Result
This review focuses on recent developments in NLCs for brain targeting of bioactives with special attention to their surface modifications, formulation aspects, pharmacokinetic behavior, and effectiveness for treating a variety of brain disorders.
Conclusion
Poorly water-soluble bioactive substances’ physicochemical properties and behavior, such as aqueous dispersibility and oral bioavailability, can be greatly improved using lipid nanocarriers. Due to the brain's complicated structure and numerous protective systems, drug distribution to the brain has remained a difficult problem for scientists. The employment of an appropriate nanocarrier technology and an alternate drug delivery method, such as nose-to-brain drug delivery, could overcome the problem of brain targeting and increase the therapeutic effectiveness of CNS-acting medications. The pharmaceutical business has recently transformed various innovative drug delivery methods that address the drawbacks of conventional drug delivery systems and offer a good benefit-to-risk ratio.
... According to Leonyza and Surini (2019), a good suspension has a zeta potential value that is more positive than +30 mV or more negative than -30 mV. Five formulas of TTOloaded NLCs initially showed a negative surface charge because the system had a negatively charged lipid (Kaur et al., 2015, Surini et al., 2020, as evident from the zeta potentials in the range of -12.5 to -14.7 mV. The negative surface charge formed an electrical barrier on the particle's surface, which, through the repulsion mechanism, contributes to the physical stability of the nanodispersion (Patil et al., 2016). ...
Context: Tea tree oil (TTO) is an essential oil derived from Melaleuca alternifolia, with high antimicrobial and antifungal potential. Unfortunately, its topical antifungal efficacy is limited because it is volatile, thermolabile and easily oxidized. A formulation has been developed to overcome this problem by encapsulating TTO in a nanostructured lipid carrier (NLC).
Aims: To determine the effect of the liquid to solid lipid ratio on the physicochemical properties and the stability of TTO-loaded NLC.
Methods: Five formula of TTO-loaded NLCs were produced by high shear homogenization method and characterized according to their particle size, size distribution, polydispersity, zeta potential, thermal characteristics, X-ray diffraction, and terpinen-4-ol concentration. In addition, a stability study was conducted by observing its physical and chemical characteristics during storage in the refrigerator (4 ± 2°C) and at room temperature (27 ± 2°C) for six months.
Results: The resulting TTO-loaded NLC had an average droplet size under 400 nm. The particle size increases with increasing amount of liquid lipid in the formula. There were insignificant changes in organoleptic properties, polydispersity index, zeta potential and terpinene-4-ol concentration during stability study for six months. However, the particle size slightly increased during the six months of storage. Furthermore, the NLC 3, which formulated with a 25:95 ratio liquid to solid lipid, was be chosen as the best formula, since it demonstrated the best physicochemical characteristic and stability.
Conclusions: TTO-loaded NLC with good physicochemical characteristics and stability has been successfully developed. In addition, NLC 3 is considered as the best NLC formula, which exhibits characteristics and stability that meet the requirements.
... Figure 6 [77-78] illustrates a few of NLC's advantages. Table 4 [79][80] contains a list of manufactured goods, their manufacturers, and their applications. Figure 6 Advantages of NLC's [77][78] ...
Cosmetics attract most age groups from teenagers to old age. Cosmetic goods now contain a variety of nanoparticle and nanomaterial types. Nano cosmeceuticals have changed the era of cosmetics as they have advanced delivery mechanisms with task specifications. They are used in nail, hair, lip, and skin care products by cosmetic giants including Estee Lauder, L’oreal, Nivea, Zelens, and Derma Swiss, etc., and have patented the use of dozens of "nanosome particles.” The global market for cosmetics using nanotechnology is worth millions of dollars and increasing at 7.14% annually. Liposomes, niosomes,nanostructured lipid carriers, solid lipid nanoparticles, gold nanoparticles, nanoemulsions, and nanosomes are novel nanocarriers that are now used in a variety of cosmeceuticals for drug delivery to achieve site specification, improved stability, biocompatibility, extended action, and increased drug-loading capacity. In this chapter use of various nanocarriers in cosmetic applications with their safety concerns will be discussed.
... The liquid lipids commonly used are natural or synthetic oils such as oleic acid, castor oil and mustard oil. 17 According to Krasodomska et al. (2016), the use of seed oil with beeswax in the NLC system in ratio 1:3 had good stability and particle size. 18 Solid lipids such as beeswax have stable physical properties but their ability to entrap active ingredients is low, so it is necessary to combine it with other lipid to make it more amorphous. ...
Background:
Candlenut oil (Aleurites moluccana L. Willd), which is also called Aleurites moluccana Seed (AMS) oil, is empirically effective as a hair growth agent, it is an unstable substance. Nanostructured Lipid Carrier (NLC) is a delivery system that is proven to increase the effectiveness and stability of the material, and the usage of solid lipid combination: beeswax-oleum cacao can produce good NLC characteristics.
Objective:
To determine the effectiveness of NLC_AMS oil with different combination of beeswax-oleum cacao (100:0; 50:50; 25:75; and 0:100) as a hair growth agent, using rats as subjects.
Methods:
NLC-AMS oil was made using 20% of total lipid with 5% AMS oil as liquid lipid and 15% solid lipid; combinations of beeswax-oleum cacao were of different ratios (100:0; 50:50; 25:75; and 0:100). NLC was made by High Shear Homogenization (HPH) method. Hair growth activity test carried out on male white rats using the research methods of Yoon (2010).
Results:
The addition of oleum cacao as a solid lipid did not affect the pH, but increased the consistency and decreased the particle size of NLC- AMS oil. There was a relationship between the characteristic of NLC and the hair growth activity test: the small particle size and low viscosity had greater hair growth activity.
Conclusion:
The usage of solid lipid combination: beeswaxoleum cacao can produce better NLC characteristics and had higher hair growth activity than the formulas that used single lipid.
... Differential scanning calorimetry Differential scanning calorimetry (DSC) is generally used to obtain information about the physical and energy properties of a compound or formulation. Based on physical or chemical sample changes, the DSC technique measures the loss or gain of heat in samples as a function of temperature [40] . Fan was successfully encapsulated in lipids in an amorphous state. ...
Background
Presently, the number of patients with lung cancer ranks second among all different cancers in the world. As a natural derivative, 7-O-( o -CF 3 -benzyl)-Fan has good anti-lung cancer activity but poor aqueous solubility. Thus, 7-O-( o -CF 3 -benzyl)-Fan-loaded solid lipid nanoparticles [7-O-( o -CF 3 -benzyl)-Fan-SLN] were prepared, and their anti-lung cancer activity in vivo and in vitro was evaluated.Results7-O-( o -CF 3 -benzyl)-Fan-SLN was prepared using low-temperature curing methods. TEM images indicated that 7-O-( o -CF 3 -benzyl)-Fan-SLN was quasi-circular. The average size of the prepared nanoparticles was 45.3 ± 4.8 nm, the polydispersity index (PDI) was 0.16, the zeta potential was -21.6 ± 2.4 mV, and the particles had high stability for at least 35 days at room temperature. IR, XRD, and DSC results showed that 7-O-( o -CF 3 -benzyl)-Fan was successfully encapsulated in lipid materials with a high entrapment efficiency of 87.98% and a drug loading of 5.18%. The IC 50 value of 7-O-( o -CF 3 -benzyl)-Fan-SLN against A549 cells was more than 2.37 times lower than that of unloaded 7-O-( o -CF 3 -benzyl)-Fan after treatment for 48 h. Flow cytometry results showed that the apoptosis rate of A549 cells was 39.61% after treatment with 2 µg/mL 7-O-( o -CF 3 -benzyl)-Fan-SLN. A nude mouse model was also used to evaluate the anticancer activities of 7-O-( o -CF 3 -benzyl)-Fan-SLN, and the results indicated that the loaded particles had an obvious anti-lung cancer effect with an inhibitory rate of 71.12% at 5 mg/kg. Moreover, western blot results showed that 7-O-( o -CF 3 -benzyl)-Fan-SLN could induce tumor cell apoptosis by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway in nude mice.Conclusions
These results indicate that the prepared solid lipid 7-O-( o -CF 3 -benzyl)-Fan nanoparticles show obvious anti-lung cancer activities and have promising prospects as potential carriers for lung cancer treatment.
... NLCs were exploited as an auspicious delivery system via different routes for various purposes, such as chemotherapy, gene therapy, brain targeting, and food preservation (Naseri et al., 2015). The advantages of NLCs include their abilities to entrap lipophilic and hydrophilic dugs, to control drug release, and to enhance drug stability and the fact that organic solvents are not necessarily needed in their formulations (Kaur et al., 2015). ...
Oral squamous cell carcinoma (OSCC) is the most common epithelial tumor of the oral cavity. Gingival tumors, a unique type of OSCC, account for 10% of these malignant tumors. The antineoplastic properties of statins, including pitavastatin (PV), and the essential oil of the Pinus densiflora leaf (Pd oil) have been adequately reported. The goal of this investigation was to develop nanostructured lipid carriers (NLCs) containing PV combined with Pd oil and to determine their cytotoxicity against the cell line of human gingival fibroblasts (HGF-1). A central composite quadratic design was adopted to optimize the nanocarriers. The particle size and stability index of the nano-formulations were measured to evaluate various characteristics. TEM analysis, the entrapment efficiency, dissolution efficiency, and the cytotoxic efficiency of the optimized PV-loaded nanostructured lipid carrier drug delivery system (PV-Pd-NLCs) were evaluated. Then, the optimal PV-Pd-NLCs was incorporated into a Carbopol 940® gel base and tested for its rheological features and its properties of release and cell viability. The optimized NLCs had a particle size of 98 nm and a stability index of 89%. The gel containing optimum PV-Pd-NLCs had reasonable dissolution efficiency and acceptable rheological behavior and acquired the best cytotoxic activity against HGF-1 cell line among all the formulations developed for the study. The in vitro cell viability studies revealed a synergistic effect between PV and Pd oil in the treatment of gingival cancer. These findings illustrated that the gel containing PV-Pd-NLCs could be beneficial in the local treatment of gingival cancer.
... This environment is beneficial for trapping of NLs. Some glyceride lipids present in NLCs may accelerate the entrance into the follicles/sebaceous glands [53] .Andthis is agreeing with our formulation RCIE-NLCs. As for the effect of RCIE-NLCs on the levels of FSH and LH, results of statistical analysis showed significant decrease (P≤0.01)in the level of FSH in group E (3.2116) mlU/ml compared with groups B and D (4.0688 and3.9974 ) mlU/ml respectively, and showed significant increase (P≤0.01) with group C (2.5556)mlU/ml, as for the level of LH the results of statistical analysis showed significant decrease (P≤0.01) ...
... In NLCs, both solids and liquid lipids are used, and since their structures are different, they are unable to form a perfect crystal. A matrix with this arrangement has many imperfections, which allows more drugs in molecular form and in amorphous clusters to be accommodated [191][192][193]. The solid matrix of NLCs reduces particle coalescence and allows drugs to be more strongly immobilized than in emulsions [194]. ...
Vaccination is still the most cost-effective way to combat infectious illnesses. Conventional vaccinations may have low immunogenicity and, in most situations, only provide partial protection. A new class of nanoparticle-based vaccinations has shown considerable promise in addressing the majority of the shortcomings of traditional and subunit vaccines. This is due to recent breakthroughs in chemical and biological engineering, which allow for the exact regulation of nanoparticle size, shape, functionality, and surface characteristics, resulting in improved antigen presentation and robust immunogenicity. A blend of physicochemical, immunological, and toxicological experiments can be used to accurately characterize nanovaccines. This narrative review will provide an overview of the current scenario of the nanovaccine.
... NLC (Nanoparticle Lipid Carrier) merupakan suatu sistem penghantaran obat dari golongan nanopartikel lipid (1). NLC tersusun oleh lipid padat, lipid cair dan emulsifier (2). NLC dikembangkan untuk mengatasi beberapa kelemahan dari generasi sebelumnya, yaitu SLN (Solid Lipid Nanopartikel). ...
NLC (Nanostructured Lipid Carrier) merupakan generasi kedua dari SLN (Solid Lipid Nanopartikel). Salah satu metode yang dapat digunakan untuk pembuatan NLC adalah HPH (High Shear Homogenization). Waktu pengadukan merupakan salah satu faktor yang mempengaruhi ukuran partikel NLC. Tujuan dari penelitian ini adalah melakukan analisa pengaruh variasi waktu pengadukan terhadap karakteristik fisik NLC. Variasi lama pengadukan yang diamati adalah 26 menit-5 siklus (sampel A) ; 30 menit-6 siklus (sampel B) ; 34 menit-7 siklus (sampel B). Ketiga sampel uji dibuat menggunakan kecepatan 5000 rpm. Karakteristik fisik yang diamati meliputi ukuran partikel, indeks polidispersitas, pH dan viskositas. Data yang didapatkan dianalisa secara statistik menggunakan One Way Anova. Hasil uji ukuran partikel menunjukkan bahwa ketiga sampel memiliki ukuran partikel yang memenuhi spesifikasi. Ukuran partikel ketiga sampel berada pada rentang 137,23 – 147,77 nm. Sampel yang memiliki ukuran partikel paling kecil adalah sampel B. Namun, sampel B memiliki indeks polidispersitas yang lebih besar daripada sampel A dan B, yaitu 0,452 ± 0,007. Berdasarkan uji organoleptis, diketahui bahwa ketiga sampel tidak memiliki perbedaan. Ketiganya memiliki warna putih, beraroma sedikit lemak dan konsistensi encer / cair. Uji pH menunjukkan bahwa pH ketiga sampel sama, yaitu 6,85-6,87. Berdasarkan uji viskositas ketiga formula memiliki viskositas yang berbeda. Sampel yang memiliki viskositas paling tinggi adalah sampel B dengan nilai 55,30 ± 0,26 cP. Walaupun memiliki nilai viskositas berbeda, tetapi ketiga formula memiliki konsistensi yang sama, yaitu encer. Waktu pengadukan yang terpilih adalah 26 menit dengan 5 siklus karena lebih efisien dari segi waktu dibandingkan waktu pengadukan yang lain. Kata kunci: karakteristik fisik, NLC, waktu pengadukan
... Type of NLC model along with characteristics NLC type Characteristics References Imperfect crystal types -Nanoemulsion is formed by blending SL(solid lipid) & LL (liquid lipid) followed by cooling and highly disorder matrix formed due to crystallization process -characterized by low liquid lipid -Disordered matrix contain more space due to gap between [11] NLC type Characteristics References fatty acid chain which will accompany more drug -NLC matrix does not form a high order structure due to different chain lengths of fatty acid & other glycerol Multiple carrier types -It is Oil/fat/water system -In the solid matrix, the oil compartment distributed -High drug solubility in nanosized lipid oil compartment -A high concentration of liquid lipid is used as a drug that has poor solubility in solid lipid -Drug entrapment is more -Prolong release is achieved because of being surrounded by a solid lipid matrix -Drug leakage minimized [12,13] Amorphous types -Mixing of special lipid to form amorphous state (e.ghydroxyoctacosanyl hydroxyl stearate or isopropyl myristate) -Drug leakage minimized due to crystallization of lipid matrix [14] Fig. 1. Different types of NLC [15] 2. NLC FABRICATION ...
Background: The advanced development of lipid nanocarrier contributes a lot to the domain of therapeutic effectiveness of the drug. However the parameter such as drug loading, drug release, stability, and targeting influence much more towards the limitation of many lipid nanocarriers. The Nanostructured lipid carrier, the second generation of lipid carrier has more promising advantages over others and have tremendous targeting ability to skin for drug administration. Objective: The present review paper focus to understand the different fabrication technique, impact of lipid and surfactant on formulation effectiveness, characterization of formulation, and Crystalinity concept of lipid which have an impact on stability & drug loading. Focus on a parameter such as Transepidermal water loss , skin occlusion, and hydration which determine the ability of the carrier to target the skin. Hence the effectiveness of the drug improved. This review also focused on patents based on Nanostructured lipid carriers. Method of preparation: many methods have been adopted to prepare Nanostructured lipid carriers and among all High-pressure homogenization method is considered as best one. Conclusion: Because of numerous advantages of this carrier system such as biocompatibility of lipid, high drug encapsulation, stability over others, it is considered as a major focused area for researchers. The new domain of Nanostructured lipid carrier is transdermal drug administration by targeting the skin; hence more research is focused on topical preparation. However, toxicity must have to be studied in humans. So by considering all factors one can rename it as “smart nano lipid carrier".
... They are made up of a range of spatial lipids such as glycerides, and they feature unstructured crystals as well as extended distances between fatty acid chains in the glyceride components, thereby allowing for more drug accommodation [13]. Although NLCs possess significant properties, they have also been associated with cytotoxic effects, low stability, irritation, and sensitizing action of surfactants [22,23]. The NLCs are further classified into three sub-types: amorphous, multiple, and imperfect. ...
Combating multiple drug resistance necessitates the delivery of drug molecules at the cellular level. Novel drug delivery formulations have made it possible to improve the therapeutic effects of drugs and have opened up new possibilities for research. Solid lipid nanoparticles (SLNs), a class of colloidal drug carriers made of lipids, have emerged as potentially effective drug delivery systems. The use of SLNs is associated with numerous advantages such as low toxicity, high bioavailability of drugs, versatility in the incorporation of hydrophilic and lipophilic drugs, and the potential for production of large quantities of the carrier systems. The SLNs and nanostructured lipid carriers (NLCs) are the two most frequently used types of nanoparticles. These types of nanoparticles can be adjusted to deliver medications in specific dosages to specific tissues, while minimizing leakage and binding to non-target tissues.
... Nanostructured lipid carriers (NLCs), a new generation of lipid nanoparticles, were designed to address some of the drawbacks of solid lipid nanoparticles (SLNs). NLCs include both solid and liquid lipid matrix [24]; this results in a matrix with a lower ordered structure containing several imperfections, which boosts drug entrapment and decreases drug leakage [25]. Due to their lipophilicity, NLCs have been utilized to deliver bioactive constituents to the brain [26]. ...
This research aimed to design, optimize, and evaluate berberine-laden nanostructured lipid carriers overlaid with chitosan (BER-CTS-NLCs) for efficient brain delivery via the intranasal route. The nanostructured lipid carriers containing berberine (BER-NLCs) were formulated via hot homogenization and ultrasonication strategy and optimized for the influence of a variety of causal variables, including the amount of glycerol monostearate (solid lipid), poloxamer 407 (surfactant) concentration, and oleic acid (liquid lipid) amount, on size of the particles, entrapment, and the total drug release after 24 h. The optimal BER-NLCs formulation was then coated with chitosan. Their diameter, in vitro release, surface charge, morphology, ex vivo permeability, pH, histological, and in vivo (pharmacokinetics and brain uptake) parameters were estimated. BER-CTS-NLCs had a size of 180.9 ± 4.3 nm, sustained-release properties, positive surface charge of 36.8 mV, and augmented ex-vivo permeation via nasal mucosa. The histopathological assessment revealed that the BER-CTS-NLCs system is safe for nasal delivery. Pharmacokinetic and brain accumulation experiments showed that animals treated intranasally with BER-CTS-NLCs had substantially greater drug levels in the brain. The ratios of BER brain/blood levels at 30 min, AUCbrain/AUCblood, drug transport percentage, and drug targeting efficiency for BER-CTS-NLCs (IN) were higher compared to BER solution (IN), suggesting enhanced brain targeting. The optimized nanoparticulate system is speculated to be a successful approach for boosting the effect of BER in treating CNS diseases, such as Alzheimer’s disease, through intranasal therapy.
... Aujourd'hui, de nombreuses techniques ont été développées afin de produire des NLC. 177 La méthode est choisie en fonction de la solubilité et la stabilité de la drogue à encapsuler. Il est également nécessaire qu'elle soit compatible avec la matrice lipidique utilisée. ...
Nanoparticules lipidiques pour la délivrance ciblée de chélateurs du cuivre : application à la maladie de Wilson. La maladie de Wilson est l’une des principales anomalies génétiques du métabolisme du cuivre chez l’homme. Des mutations au niveau du gène codant pour une ATPase à cuivre (ATP7B) entrainent une accumulation de cuivre à un niveau toxique dans les cellules du foie (hépatocytes) et le cerveau. Les traitements actuels principalement la D-Penicillamine (Trolovol®) et la triéthylènetétramine (Trientine®) sont des chélateurs de cuivre et permettent de stimuler son excrétion dans les urines. Cependant, ces traitements présentent un certain nombre d’effets indésirables entrainant une faible compliance.Précédemment au laboratoire SYMMES, un chélateur de cuivre a été développée afin de piéger efficacement le Cu(I) présent en excès dans les hépatocytes. Ce promédicament est basé sur un chélateur bioinspiré, spécifique du cuivre au degré d’oxydation +1, fonctionnalisé à des sucres N-acétyl-D-galactosamine (GalNAc) pour la reconnaissance spécifique par les récepteurs aux asialoglycoprotéines (ASGPR).Dans la cadre de ce projet de thèse, une approche originale a été envisagée et consiste à utiliser des nanoparticules lipidiques (NLC, Lipidots®) développées au laboratoire DTBS contenant un analogue lipophile d’un chélateur de cuivre et dont la surface est fonctionnalisée par des unités GalNAc pour la délivrance dans les cellules hépatiques. Une première partie de ces travaux de thèse a été consacrée à la fonctionnalisation par des GalNAC à la surface des nanoparticules. Après formulation en présence de surfactants fonctionnalisés par des GalNAc et quantification par UPLC-ELSD, l'internalisation de ces nanoparticules a été évaluée par cytométrie en flux. L'interaction de ces nanoparticules avec une lectine modèle a été réalisé par SPR en collaboration avec l'IBS. Dans une deuxième partie, l'encapsulation de chélateurs lipophiles a été évaluée par HPLC couplé à l'extraction en phase solide (SPE). L’aptitude de ces nanoparticules à libérer le chélateur et à piéger le cuivre ont été évalués sur deux types de cellules hépatiques (sauvages et sans ATP7B) en collaboration avec le laboratoire LCBM.
... This setting is useful for NL trapping. Some NLCs may speed up entry in follicles/sabaceous glands via glyceride lipids (34). And this is agreeing with our formulation RCIE-NLCs. ...
Plant-derived edible nanoparticles (PDNPs) are nano-sized membrane vesicles released by edible plants. They are non-toxic, have tissue-specific targeting properties, and can be mass-produced , to assess the effect of phytoestrogens (PEs) for treating hyperlipidemia that associated with menopause period using nanoparticles lipid carrier (NLCs) loaded with red clover isoflavones extract (RCIE) compared with hormone replacement therapy (HRT). Study was conducted using fifty adult female mice model for menopause using 4-Vinylcyclohexene dioxide (VCD) and handled as follows for 6 weeks. Two experiments were preformed, the first experiment included 20 mice divided into two groups Group A: Control group has injected 0.1 ml D.W. intraperitoneal (IP) daily. Group B: This group has injected IP daily 160 mg/kg B.W of VCD. The second experiment was included 30 mice have injected IP daily 160 mg/kg of VCD and divided into three groups (C, D and E), (10 / group) then treated with dermal sticker for six weeks: Group C: treated with dermal sticker saturated with 10ug/ kg B.W of estradiol benzoate (EB) diluted with virgin coconut oil (VCNO). Group D: treated with dermal sticker saturated with 0.1 of VCNO. Group E: treated with dermal sticker saturated with 0.1ml of RCIE-NLCs. The results of statistical analysis showed a significant increase in the level of TC, TG, LDL, and VLDL in group VCD. While RCIE-NLCs had a clear effect and significant decreased in the TG, TC, LDL and VLDL cholesterol compared to groups VCD and EB, and significant increase in the HDL-C in group RCIE-NLCs compared to groups VCD and EB. The results of this study revealed that administration of RCIE-NLCs shows an effective to regulation of lipids metabolism disorders due to hormonal changes that associated with menopausal transition via impact of VCD.
... There should be an in vitro in vivo correlation between drug release and the environment of the release site. The composition of nanoparticles and their enzymatic degradation are also relatable to some extent [31]. ...
The lipids mainly oils, fats, waxes and phospholipids are of substantial importance in the development and functioning of cosmetic products. The lipid nanoparticles-based cosmetic product is highly capable of protecting the skin against harmful radiations and is utilized for anti-aging therapy. Naturally derived antioxidants such as carotenoids, retinoids and tocopherols could be employed for their antioxidant properties as therapeutics and skincare active moieties in cosmetic products. Such a lipid nanoparticles-based cosmetic formulation consisting of antioxidants are very effective against irritated and inflamed skin and very promising for treating skin disorders such as atopic dermatitis and psoriasis. Therefore, the present review provides an insight into lipid nanoparticles based cosmetics and the mechanistic of their percutaneous absorption. The manuscript discussion highlights the role of lipid nanoparticles-based cosmetics/cosmeceuticals employing active ingredients of synthetic and natural origin in alleviating dermatological disorders and enhancing skin health and appeal. Furthermore, the manuscript also updates about contemporary research studies carried on the concept of lipid nanoparticles based formulation design of cosmetic preparation and significant outcome to alleviate skin disorders.
... NLCs nowadays are widely used in topical cosmetic or dermatological follicular targeting preparations as it offers the benefits of reducing both the drug dose and the systemic side effects accompanied by oral delivery of medication (13). The increase in drug distribution to the target site within the hair follicles may result from the small size of the lipid particles that assures close connection to the stratum corneum, thus promoting drug penetration into the hair follicle (14). On the other hand, NLCs were developed as promising drug delivery carriers through the skin due to its lipid nature and biocompatibility. ...
Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (− 31.4 to − 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP-NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism.
... Furthermore, isoflavones play an important role in preventing menopause-related disorders and chronic diseases, such as heart diseases, cancer, and diabetes (Esteves and Monteiro,2001). Intact nanoparticles sized above 100nm are not considered to permeate the skin surface because of their dimensions and rigidity (Cevc,2004 (Sarabjot et al.,2015). And this is agreeing with our formulation RCIE-NLCs. ...
Introduction: Plant-derived edible nanoparticles (PDNPs) are nano-sized membrane vesicles released by edible plants. They are non-toxic, have tissue-specific targeting properties, and can be mass-produced.
... This environment is beneficial for trapping of lipid nanoparticles. Some glyceride lipids present in NLCs may accelerate the entrance into the follicles/sebaceous glands (Sarabjot et al., 2015) and this is agreeing with our formulation GE-NLCs. ...
... This environment is beneficial for trapping of lipid nanoparticles. Some glyceride lipids present in NLCs may accelerate the entrance into the follicles/sebaceous glands (Sarabjot et al., 2015) and this is agreeing with our formulation GE-NLCs. ...
Plant-derived edible nanoparticles (PDNPs) are nano-sized membrane vesicles released by edible plants. They are non-toxic, have tissue-specific targeting properties, and can be mass-produced. The study aimed to assess the effect of gingerols to decreased the levels of total cholesterol (TC), triglycerides (TG) and lipoproteins (HDL, LDL, VLDL) levels that associated with menopausal transition using nanoparticles lipid carrier (NLCs) loaded with gingerols extract (GE-NLCs). The study was conducted using thirty adult female mice divided into three groups (10 mice/ group) and handled as follows for 6 weeks. Group A: Control group has injected 0.1 ml D.W intraperitoneal (IP) daily. Group B: This group has injected IP daily 160 mg/ kg B.W of 4-Vinylcyclohexene dioxide (VCD) for two weeks as model for menopause, group C: Animals in this group were administered 160 mg /kg B.W of VCD IP daily for two weeks for inducing menopause, then shaved at the last third of the back and treated with dermal sticker saturated with 0.1ml of GE-NLCs for six weeks. A gingerols extract standardized by High-performance liquid chromatography (HPLC) to contain (18.3) mg/g of gingerols. The characterization of GE-NLCs was done by transmission electron microscopy (TEM), Scanning probe microscopy (SPM), Zeta potential. TEM images showed that shape of particles was mostly spherical and few cylindrical with average diameter (64.31) nm. SPM images showed the average grain size was (42.81) nm. Encapsulation Efficiency (EE) was 85%. Zeta potential was (-42.9) Mv. The results of statistical analysis showed a significant decrease (P0.01) in the level of estrogen in group B (23.767) ng/ml, compared with group A (33.154) ng/ml and significant increase in the estrogen level in group C (29.742) ng/ml compared with group B. While for levels of lipids, the result of statistical analysis showed a significant increase in the level of TC in group B (101.94) mg/dl, compared with group A (80.00) mg / dl, and significant decreased in group C (80.86) mg/dl, compared with group B and significant increase (P0.01) in the level of TG in group B (79.400) mg/dl, compared with group A (54.200) mg/dl and significant decrease in group C compared (61.158) mg/dl, compared with group B. and The result s of statistical analysis showed a significant decreased (P0.01) in the level of HDL in group B (18.800) mg/dl, compared with group A (23.001) mg/dl and no significant difference in group C (18.168) mg/dl, compared with group B and significant increase in the level of LDL in group B (66.88) mg/dl, compared with group A(50.36) mg/dl and significant decreased in group C (44.71) mg/dl, compared with group B and results of statistical analysis showed a significant increased (P<0.01) in the level of VLDL in group B (16.62) mg/dl, compared with group A (10.84) mg/dl and significant decreased in group C (11.90) mg/dl, compared with group B. Conclusion: The results of this study revealed that administration of GE-NLCs shows an effective to regulation of lipids metabolism disorders due to hormonal changes that associated with menopausal transition via impact of VCD.
... This environment is beneficial for trapping of lipid nanoparticles. Some glyceride lipids present in NLCs may accelerate the entrance into the follicles/sebaceous glands (Sarabjot et al., 2015) and this is agreeing with our formulation GE-NLCs. ...
... DSC is usually adopted to gain information about the physical properties of drugs, polymers, and formulations. It measures the heat gain or loss in samples as a function of temperature [45]. The DSC thermograms of free DXL, SF, physical mixture, and optimized DXL-loaded SF-NPs are shown in Figure 2B. ...
Despite decades of research, breast cancer therapy remains a great challenge. Docetaxel is an antimicrotubule agent that is effectively used for the treatment of breast cancer. However, its clinical use is significantly hampered by its low water solubility and systemic toxicity. The current study was designed to prepare docetaxel (DXL)-loaded silk-fibroin-based nanoparticles (SF-NPs) and to screen their potential antitumor activity against breast cancer cell lines. DXL-loaded SF-NPs were prepared using a nanoprecipitation technique and were evaluated for particle size, zeta potential, entrapment efficiency, and in vitro release profile. In addition, DXL-loaded SF-NPs were screened for in vitro cytotoxicity, cellular uptake, and apoptotic potential against MCF-7 and MDA-MB-231 breast cancer cell lines. The prepared DXL-loaded SF-NPs were 178 to 198 nm in diameter with a net negative surface charge and entrapment efficiency ranging from 56% to 72%. In vitro release studies exhibited a biphasic release profile of DXL from SF-NPs with sustained drug release for 72 h. In vitro cell studies revealed that entrapment of DXL within SF-NPs significantly improved cytotoxic potential against breast cancer cell lines, compared to the free drug, and enhanced cellular uptake of DXL by breast cancer cells. Furthermore, the accumulation in the G2/M phase was significantly higher in cells treated with DXL-loaded SF-NPs than in cells treated with free DXL. Collectively, the superior antitumor activities of DXL-loaded SF-NPs against breast cancer cells, compared to free DXL, could be ascribed to improved apoptosis and cell cycle arrest. Our results highlighted the feasibility of using silk fibroin nanoparticles as a nontoxic biocompatible delivery vehicle for enhanced therapeutic outcomes in breast cancer.
For the delivery of the drug, the oral route is the most preferable due to ease of administration. However, the effective delivery of poorly aqueous soluble drugs is very challenging for the pharmaceutical scientist which leads to a low drug permeation profile across the biological membrane, poor drug bioavailability, and ultimately low therapeutic profile with less patient comfort. The inclusion of a therapeutic agent into the nanostructured-based lipid carrier can improve the limitation associated with the poorly soluble drug and it includes better drug therapeutic, pharmacokinetic profile, and controlled drug release up to a longer duration of time which causes patient compliance. Nanostructure lipid carriers (NLCs) are nanosized-based carrier systems which comprise solid lipid matrix combined with liquid lipids and surfactants. The aim of the paper is to explore the various advantages of formulation technology along with the characterization parameter of the NLCs and also report the clinical finding of the investigated NLCs for oral drug delivery system. This paper also highlighted the various patents on the NLCs.
The present study aims to develop a delivery system that can carry small interference RNA (siRNA) with small-molecule chemotherapeutic drugs, which can be used in cancer treatment. The drug delivery system combines the advantages of a therapeutic agent with two different mechanisms to ensure that it is used efficiently for cancer therapy. In this study, a nanostructured lipid carrier system was prepared, Docetaxel was loaded to these systems, and the Eph siRNA was adsorbed to the outer surface. In addition, DOTAP was added to the lipophilic phase to load a positive charge on the lipidic structure for interaction with the cells. Moreover, characterization, cytotoxicity, and transfection procedures were performed on the whole system. This candidate system was also compared to Taxotere, which is the first approved Docetaxel-containing drug on the market. Given the results, it was determined that the particle size of NLC-DTX was 165.3 ± 3.5 nm, the ζ potential value was 38.2 ± 1.7 mV, and the PDI was 0.187 ± 0.024. Entrapment efficacy of nanoparticles was found to be 92.89 ± 0.21%. It was determined that the lipidic system prepared in vitro release analyses were able to provide sustained release and exhibit cytotoxicity, even at doses lower than the dose used for Taxotere. The formulations prepared had a higher level of effect on cells when compared with pure DTX and Taxotere, but they also exhibited time-dependent cytotoxicity. It was also observed that the use of Eph siRNA together with the chemotherapeutic agent via formulation also contributed to this cell death. The results of the present study indicate that there is a promising carrier system in order to deliver hydrophilic nucleic acids, such as siRNA, together with lipophilic drugs in cancer treatment.
Background:
A nanostructured lipid carrier (NLC) is a nanoparticulate carrier system consisting of solid lipids, liquid lipids, surfactants, and water. NLCs are second-generation lipid nanocarriers, gained continuous significance in recent times, and possess better physical stability, increased drug loading, improved permeability, and bioavailability. They are considered superior to many other traditional lipid-based nanocarriers such as nanoemulsion, liposomes, and solid lipid nanoparticles (SLN) and have emerged as an alternative to first-generation nanoparticles (SLN). NLCs have significant potential in the pharmaceutical industry due to their extensive beneficial effects, like drug targeting, enhanced bioavailability, and their wide positive benefits.
Objective:
The primary aim of this review was to study and explore the Nano lipid carrier, its advantages, patent preferences, and advancement of NLCs use in nose-to-brain drug delivery
Methods:
The objective of this study was to conduct a literature review on the development of NLC for nose-to-brain drug delivery. The review focused on NLC, its significant role in nose-to-brain delivery, and relevant patents. To achieve this goal, different review articles searched, were studied, and summarized from various sources such as research articles, review articles, books, scientific reports, and patents.
Conclusion:
This review article discusses the potential benefits of NLCs in brain-targeting drug delivery through the intranasal route and key aspects of NLCs, including their structure composition, formulation technique, and characterization, which are crucial for developing a reliable drug delivery.
Sunlight, despite its benefits, can pose a threat to the skin, which is a natural protective barrier. Phototoxicity caused by overexposure, especially to ultraviolet radiation (UVR), results in burns, accelerates photoaging, and causes skin cancer formation. Natural substances of plant origin, i.e., polyphenols, flavonoids, and photosynthetic pigments, can protect the skin against the effects of radiation, acting not only as photoprotectors like natural filters but as antioxidant and anti-inflammatory remedies, alleviating the effects of photodamage to the skin. Plant-based formulations are gaining popularity as an attractive alternative to synthetic filters. Over the past 20 years, a large number of studies have been published to assess the photoprotective effects of natural plant products, primarily through their antioxidant, antimutagenic, and anti-immunosuppressive activities. This review selects the most important data on skin photodamage and photoprotective efficacy of selected plant carotenoid representatives from in vivo studies on animal models and humans, as well as in vitro experiments performed on fibroblast and keratinocyte cell lines. Recent research on carotenoids associated with lipid nanoparticles, nanoemulsions, liposomes, and micelles is reviewed. The focus was on collecting those nanomaterials that serve to improve the bioavailability and stability of carotenoids as natural antioxidants with photoprotective activity.
The central nervous system, or CNS for short, is among the most significant bodily organs because of what it does for the human body. Therefore, a decline in its function may lead to a variety of maladies of the CNS or other body systems that are highly significant. Drug delivery technologies based on lipids called nanostructured lipid carriers (NLCs) have received much study. The creation of NLCs, or nanostructured lipid carriers, was done. The diverse delivery methods for nano-based systems include parenteral, transdermal, ophthalmic, oral, and topical. The creation of NLCs included blending spatially incompatible liquid and solid lipids. Improved bioavailability and higher solubility are drug therapy's key benefits over traditional carriers of NLCs. NLCs used for brain targeting NLCs for CNS diseases (glioma/brain cancer, ischemic stroke, Alzheimer's disease, Parkinson's disease, epilepsy, migraine, Hodgkin's disease, schizophrenia, and multiple sclerosis) are discussed in this review along with their benefits and drawbacks. NLCs method, the most common categories include imperfect, amorphous, and multiple types. Solid lipids, liquid lipids, surfactants, and other excipients are also employed in NLCs. The methods used to create NLCs include high-pressure homogenization, solvent emulsification/evaporation, micro-emulsification, ultrasonication, supercritical fluid, and solvent injection. In recent years, it has drawn more and more interest.
The oral route is one of the most preferred routes of administration because of its convenience and safety. Nanostructured lipid carriers (NLCs) are the second-generation nanosize solid lipid nanocarriers that are composed of solid lipids, liquid lipids, and surfactants. The lipid matrix of NLCs has an imperfect structure which allows more drug loading. Other advantages offered by NLCs include biocompatibility, biodegradability, and high encapsulation efficiency. They are considered potential nanocarriers in oral drug delivery and have particle size in the range of 50–300 nm. NLCs have shown improved oral bioavailability of lipophilic drugs. They also bypass first-pass metabolism and inhibit the P-glycoprotein (P-gp) efflux mechanism of drugs. This review mainly highlights the role of NLCs in the oral delivery of drugs and different barriers that have to be overcome to achieve drug delivery by oral route.
Graphical abstract
Captopril loaded nanostructured lipid carriers was formulated by using homogenization followed by sonication technique. For selecting formulation excipients like solid lipid, liquid lipid and surfactant solubility studies was done and by this studies it was concluded that, Compritol, Oleic acid and tween 80 shows highest solubility. Hence these three are selected for further formulation of NLC.
NLC was formulated and optimized using response surface methodology i.e, CCRD and the model is subjected to 20 runs. Optimization can be done by fixing three independent variables and three responses. The independent variables are concentration of solid lipid (A), liquid lipid (B) and surfactant(C) and the responses are particle size, zeta potential and poly dispersity index.
In order to get the optimized formulation, the desirability function was run using Design-Expert software V 11.0. Software optimization process and desirability criteria of response surface methodology calculate the effect of factor and its level on the each response and predicts the optimize point which represents the maximum desirability. The desired point for each response was selected on the basis of importance, which may affect the characteristics of a goal. The goal fields for every response have five option i.e within the range, target, minimum, maximum and none. An overlay plot and desirability plot were constructed to investigate the relationship between factors and response. The optimum formulae based on the criteria of minimum particle size & maximum entrapment was selected.
In-vitro drug release studies for the optimized formulation was done by using dialysis method, in the phosphate buffer of pH 7.4 and the release pattern was studied for a maximum of upto 98-99% of drug release. From this study it was reported that, the release rate from the NLC was observed upto 12 hrs and it concluded that the NLC is releasing the drug at a definite intervals and it was a pre-requisite for prolonged release.
The book reviews recent developments in the field of nanomaterials science and technology. Topics covered include methods of fabrication of nanomaterials and nanocomposites, and their applications in areas such as Optoelectronics, Cosmetics, Energy Conversion Cells, Soil and Water Treatment, Agricultural Engineering, Food Sciences, Leather Production, and Photocatalysis.
Nanocomposite and their applications
Flutamide is an antagonist of testosterone, an essential hormone in male reproduction. However, the use of flutamide as a contraceptive agent for nonsurgical castration in veterinary practice remains challenging due to its poor bioavailability. Here, the flutamide-loaded nanostructure lipid carrier (FLT-NLC) was synthesized, and its biological effects were demonstrated by an in vitro blood-testis barrier model. The flutamide was incorporated into the nanostructure lipid carrier by a homogenization method resulting in a high encapsulation efficiency (99.7 ± 0.04%). The FLT-NLC was negatively charged (-27.90 ± 0.10 mV), with a nano size (182.13 ± 0.47 nm) and narrow dispersity index (0.17 ± 0.01). An in vitro release study demonstrated a slower release profile of FLT-NLC when compared with flutamide solution (FLT). The FLT-NLC at doses up to 50 μM showed no significant cytotoxic effects against mouse Sertoli cells (TM4) or mouse fibroblast cells (NIH/3T3) (p > 0.05). An in vitro blood-testis barrier with FLT-NLC demonstrated remarkable lower transepithelial electrical resistance when compared with those lacking FLT-NLC (p < 0.01). Moreover, FLT-NLC significantly decreased the mRNA expression of blood-testis barrier proteins, CLDN11 and OCLN. In conclusion, we successfully synthesized FLT-NLC and confirmed its potential antifertility effects on in vitro blood-testis barrier, thus indicating its possible application as nonsurgical contraception for male animals.
Background
Tobacco smoking is a major factor leading to cardiovascular diseases. About 48% of cardiovascular diseases occur due to cigarette smoking. Bupropion Hydrochloride is non-nicotine treatment for smoking cessation. The existing marketed formulation of bupropion have limitations like low bioavailability and extensive first-pass metabolism. In order to boost the bioavailability and increase the brain biodistribution of the drug, a colloidal drug delivery system like nanostructured lipid carriers is employed.
Methods
NLC formulation was prepared using microemulsion technique and optimized formula was developed using three-level factorial design.
Results
The particle size of the optimized formulation was 162 nm, Polydispersity index was 12.2% and zeta potential was -29.0mV. Entrapment efficiency was found to be 41.2%. SEM images show that these NLCs are spherical. In-vitro drug release study was conducted and at the end of 72 hours, 50 % of drug was released, indicates the sustained release of drug. Histopathological studies were conducted using goat nasal mucosa and results indicates that NLC formulation is non-toxic for intranasal administration.
Conclusion
Thus, through intra-nasal route an increased concentration of drug can be delivered to the brain via olfactory pathway and improve the therapeutic effect and better patient compliance in smoking cessation.
The increase in the global population demands new technologies in energy consumption and environmental changes. The energy and environment are the crucial factors for the evolvement of the human life. The advent and recent trends in nanotechnology offers promising approach in fulfilling the demands of human life. Nanotechnology is an emerging branch of science and technology which acts as a key role in environmental monitoring and energy conversion, distribution, and storage. The applications of nanoscale materials and nanoparticles in energy and environment enhance and simplify
the process flow with cost-effectiveness as well as eco-friendly approach over the current conventional methods. The applications of nanotechnology are versatile in various domains such as bioremediation, waste management, green technology, environmental monitoring, emission control, electricity production and transmission loss, solar power, etc.
The increase in the global population demands new technologies in energy consumption and environmental changes. The energy and environment are the crucial factors for the evolvement of the human life. The advent and recent trends in nanotechnology offers promising approach in fulfilling the demands of human life. Nanotechnology is an emerging branch of science and technology which acts as a key role in environmental monitoring and energy conversion, distribution, and storage. The applications of nanoscale materials and nanoparticles in energy and environment enhance and simplify
the process flow with cost-effectiveness as well as eco-friendly approach over the current conventional methods. The applications of nanotechnology are versatile in various domains such as bioremediation, waste management, green technology, environmental monitoring, emission control, electricity production and transmission loss, solar power, etc.
The present work was aimed with the objective of developing simple, precise and sensitive high performance liquid chromatographic method for simultaneous estimation of quetiapine fumarate and curcumin and to execute the developed method in the simultaneous estimation of both the drugs in nanostructured lipid carrier formulations. The method was carried out using various solvents, buffers, at different flow rates for the complete separation and estimation of both the drugs. Using ICH guidelines, the developed method was validated. After various trials the chromatographic conditions were optimized. The complete chromatographic separation and estimation of both drugs was possible using phenomenex kinetex XB-C18 100 A analytical column (3.5 μm, 4.6 mm × 150 mm) and methanol: water 70:30 v/v as a mobile phase, at the flow rate of 1.0 mL/min. Sample of 200 μL was injected and chromatogram was recorded at 290 nm in triplicates. The absorption maximum for quetiapine fumarate was found to be in 290 nm, whereas curcumin possess absorption maxima at 421 nm. The simultaneous estimation of both drugs is possible when estimated at particular single wave length. The peak response for quetiapine fumarate and curcumin was maximum at 290 nm which has been fixed for the analysis.
A series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, especially compounds 4h, 4j and 5d. Being the most potent, compound 4h showed good tubulin polymerization inhibition activity as revealed by immunofluorescence analysis and ELISA assay. Additionally, compound 4h was screened for cell cycle disturbance and apoptosis induction. Pre-G1 apoptosis and cell growth halt at the G2/M phase were discovered to be caused by it. Moreover, compound 4h induced apoptosis via p53 and Bax activation, as well as reduced the level of Bcl-2. Additionally, the most potent compound 4h was lodged on nanostructured lipid carriers (NLCs). 23 full factorial design was involved to govern the influence of the fabrication variables on the in vitro characters of the casted NLCs. F3 was picked as the optimum formula exhibiting dominant desirability value 0.805, EE% 95.6 ± 2.4, PS 222.4 ±18.7, PDI 0.23 ± 0.05 and ZP −39.2 ± 3.9 Mv. Furthermore, F3 affirmed improved solubility and release over the drug suspension. In the comparative cytotoxic activity, F3 was capable of diminishing the IC50 by around 2.15 times for pure 4h, while nearly close to the IC50 of the reference drug. Thus, NLCs could be a potential platform for boosted antitumor activity.
The development of bioactive components as a delivery system with the use of advanced nanoscience is opening new therapeutic avenues for the management of various diseases. Among recent novel applications, plant phytopharmaceuticals and nutraceuticals are the fastest growing areas of nanotechnology-based research for effective public healthcare. Bioactive compounds, either encapsulated or in entrapped form within novel drug delivery systems are reported as a booster treatment for the various chronic infections and life-threatening diseases, including cancer, cardiovascular disorders, hypertension, diabetes, asthma, malaria, microbial infections, immune disorders, and gastrointestinal disorders. Recently, considerable progress surged in understanding the factors associated with these diseases. A variety of nanoscience-based formulations such as polymeric matrix nanoparticles, aerosol inhalers/nebulizers nanoemulsion, and vesicular carrier systems including liposome, phytosome, transfersome, herbosome, ethosome, niosome, have proven valuable in the delivery of bioactive materials. Moreover, the scientific community had reported that the herbs and herbal bioactive compounds have notable recompense compared to the conventional method of delivering phytopharmaceuticals and plant extracts, with enhanced solubility, bioavailability, stability, tissue distribution, abridged toxicity, improved pharmacological efficacy, and protection from physicochemical degradation. The current chapter focuses on the carrier-based delivery of bioactive as a booster with advanced using nanoscience, such as nanoemulsion and vesicular drug delivery systems. In addition, the chapter also elaborates patented technologies along with potential bioactive products available in the market.
Cancer is a life-threatening disease that is associated with persistent tissue injury and uncontrolled cell growth. The treatments available to treat cancer include chemotherapy, surgery, and radiation therapy. These treatments are utilized in combination while the most preferred treatment is chemotherapy. Because of the non-specificity of anticancer drugs, they kill healthy cells along with cancer cells, which lead to severe side effects. To minimize such limitations associated with conventional chemotherapy, nanostructured lipids carriers (NLCs) can be developed. These are the nanocarriers consisting of a mixture of solid and liquid lipids and surfactants. Lipids utilized in the formulation of NLCs are biocompatible and biodegradable. NLCs ensure high drug payload, less drug expulsion, and more stability on storage. NLCs enhance the aqueous solubility of lipophilic anticancer drugs. Their surface modification can help to overcome drug resistance in cancer therapy. Controlled and targeted drug delivery of anticancer drugs can be possible by formulating them as NLCs. NLCs can play an important role in targeting anticancer drugs by different mechanisms. This review highlights types, formulation methods, characterization of nanostructured lipid carriers, and strategies to achieve targeted release of anticancer drugs loaded in NLCs.
Background
In recent years, the field of nanotechnology and nanomedicine has transformed the pharmaceutical industry with the development of novel drug delivery systems that overcome the shortcomings of traditional drug delivery systems. Nanostructured lipid carriers (NLCs), also known as the second-generation lipid nanocarriers, are one such efficient and targeted drug delivery system that has gained immense attention all across due to their myriad advantages and applications. Scientific advancements have revolutionized our health system, but still, brain diseases like brain tumour have remained formidable owing to poor prognosis and the challenging drug delivery to the brain tissue. In this review, we highlighted the application and potential of NLCs in brain-specific delivery of chemotherapeutic agents.
Main body
NLCs are lipid-based formulations with a solid matrix at room temperature and offer advantages like enhanced stability, low toxicity, increased shelf life, improved drug loading capacity, and biocompatibility over other conventional lipid-based nanocarriers such as nanoemulsions and solid lipid nanoparticles. This review meticulously articulates the structure, classification, components, and various methods of preparation exemplified with various research studies along with their advantages and disadvantages. The concept of drug loading and release has been discussed followed by a brief about stability and strategies to improve stability of NLCs. The review also summarizes various in vitro and in vivo research studies on NLCs encapsulated with cytotoxic drugs and their potential application in brain-specific drug delivery.
Conclusion
NLCs are employed as an important carrier for the delivery of food, cosmetics, and medicines and recently have been used in brain targeting, cancer, and gene therapy. However, in this review, the applications and importance of NLCs in targeting brain tumour have been discussed in detail stating examples of various research studies conducted in recent years. In addition, to shed light on the promising role of NLCs, the current clinical status of NLCs has also been summarized.
Graphical Abstract
The aim of the present study was to formulate and develop a Nanoparticulate drug delivery system (Nanostructured Lipid Carrier) for the treatment of Acne. The nanostructured lipid carrier was prepared by high speed and high pressure homogenizer by using different types of solid lipid, liquid lipid and concentration of surfactants. The NLC was characterized by particle size, zeta potential, polydispersity index. Stearic acid and oleic acid were used as solid lipid and liquid lipid and Pluronic F-68 was used as surfactant. The drug excipient compatibility study was performed by Fourier transform infrared spectrophotometer and the result revealed that all the excipients and drugs were compatible with each other. For the drug estimation HPLC method was developed for the combined drug Clindamycin phosphate and Nicotinamide. Formulation of nanoemulsion was prepared by high speed and high-pressure homogenization technique. This emulsion was incorporated into the gel which was prepared by using Carbopol 934P as gel base and evaluated for the In-vitro release. A factorial design was used for the evaluation and optimization of the nanoparticles. Short term stability study was performed for 30 days and there was no significant change in consistency, pH and viscosity.
Rosuvastatin calcium (ROSCa) is an anti-hyperlipidemic drug with only 20% oral bioavailability due to its low solubility and high first-pass metabolism. Therefore, the main purpose of this work was to compare solid lipid nanoparticles to nanostructured lipid carriers and evaluate their effect on solubility improvement and hence the bioavailability of a model insoluble drug.
Methodology:
Different nanosuspensions were formulated using high-speed homogenization and ultrasonication techniques, using Apifil as solid lipid and maisine as liquid lipid. The effect of different variables on quality attributes (particle size, entrapment efficiency (EE), and in vitro release) was studied using the Box-Behnken design. Then, the optimized nanoparticles were lyophilized, filled into capsules, and evaluated. Finally, the optimized formula was clinically evaluated in six healthy human volunteers.
Results:
It was observed that the variables had a great impact on EE and particle size. Nanoparticles showed maximum particles of 180.3 nm, and % EE ranged from 40.77% to 91.67%. Capsules loaded with NLCs were found to be more stable than those loaded with SLNs. The clinical study of NLCs-ROSCa showed an enhancement in the C max (8.92 ng/ml) compared to the commercial product (2.56 ng/ml) with approximately 349% relative bioavailability.
Conclusion:
ROSCa was successfully encapsulated in SLNs and NLCs. The optimized NLCs formulation showed improved quality attributes compared to SLNs. Thus, NLCs loaded formulations could be an effective oral drug delivery system to enhance the bioavailability of insoluble drugs.
Pendahuluan: Minyak nilam memiliki efek antioksidan dan peningkat penetrasi. Minyak tersebut berpotensi meningkatkan efektivitas produk sleeping mask dengan Koenzim Q10 (KoQ10) yang dimuat dalam Nanostructured Lipid Carriers (NLC) sebagai kosmetik anti-penuaan. Tujuan: Membandingkan karakteristik dan stabilitas fisik dari NLC-KoQ10 yang dimuat dalam sleeping mask dengan dan tanpa minyak nilam. Metode: Preparasi NLC-KoQ10 menggunakan metode High Shear Homogenization. NLC-KoQ10 dicampur dengan hydrogel dan minyak nilam, untuk F2. Sedangkan untuk F1 tanpa minyak nilam. Setelah itu diamati karakteristik dan stabilitas fisiknya yang meliputi organoleptik, pH, dan viskositas. Uji stabilitas fisik diamati pada suhu ruang selama 90 hari. Hasil: Uji karakteristik fisik menunjukkan bahwa F1 memiliki bau seperti oleum cacao, sedangkan F2 memiliki bau khas minyak nilam dan sedikit bau seperti oleum cacao. F1 memiliki nilai pH 6,036 ± 0,011, sedangkan F2 memiliki nilai pH 6,062 ± 0,020. Tidak ada perbedaan yang signifikan. Namun, F1 dan F2 memiliki nilai viskositas yang berbeda. F1 memiliki nilai viskositas 199,2 ± 0,7 cp, sedangkan F2 memiliki nilai viskositas 175,6 ± 7,9 cp. Uji stabilitas fisik menunjukkan bahwa F1 dan F2 memiliki skala nilai pH berkisar 6,055 - 6,336 dan viskositas 175,6 - 239,7 cp. Nilai viskositas F1 mengalami peningkatan setelah hari ke-60, sedangkan F2 pada hari ke-90. Kesimpulan: Berdasarkan uji karakteristik dan stabilitas fisik dapat disimpulkan bahwa F1 dan F2 memiliki bau dan viskositas yang berbeda, dan F2 lebih stabil daripada F1.
Nanotechnology is the science of manipulating the structural entities at nanoscale and beauty based solution industry is one of the most passionate explorer of nanostructures which contemplated as a huge boon in the cosmeceuticals for various beauty solutions. Exploration of nanostructures is escalating in the cosmeceuticals due to limitations coupled with the conventional products. Although, cosmeceutical is not FDA approved terminology but designate the personal care products at the borderline between cosmetics and pharmaceuticals. Emerging trends in cosmetics frequently include nano-sized structure novel carriers (like nano-emulsions, nanocapsules, nanosomes, niosomes or liposomes) consisting of traditional cosmetic materials. Nanocosmeceuticals contains naturally derived ingredients and synthetics too, but all contains functional ingredients with their therapeutic, disesase-flighting and healing properties. Nanocosmeceuticals has been developing with significant pace over recent years, extensively used to address beauty solutions. Nanocarriers are novel nanostructure having the advantages of effective penetration in skin, controlled site specific targeting, higherstability and entrapment efficiency. The current review put light on various aspects of nanostructure candidates in cosmetics including its synthesis, nanocarriers, regulations potentialconcerns and future trends.
Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as a carrier for curcumin (CRM). The CRM-loaded NLC developed as a particle with the size of 146.8 nm, a polydispersity index of 0.18, an entrapment efficiency (EE) of 90.86%, and the zeta potential (ZP) of À21.4 mV. Besides, the increased cytotoxicity of CRM-NLC than that of CRM to astrocytoma-glioblastoma cell line (U373MG) in the cancer cell lines was observed. Results of biodistribution studies showed higher drug concentration in brain after intranasal administration of NLCs than PDS. The results of the study also suggest that CRM-NLC is a promising drug delivery system for brain cancer therapy.
Unlabelled:
Colloidal nanocarriers, in their various forms, have the possibility of providing endless opportunities in the area of drug delivery. The current communication embodies an in-depth discussion of colloidal nanocarriers with respect to formulation aspects, types, and site-specific drug targeting using various forms of colloidal nanocarriers with special insights to the field of oncology. Specialized nanotechnological approaches like quantum dots, dendrimers, integrins, monoclonal antibodies, and so forth, which have been extensively researched for targeted delivery of therapeutic and diagnostic agents, are also discussed. Nanotechnological patents, issued by the U.S. Patent and Trademark Office in the area of drug delivery, are also included in this review to emphasize the importance of nanotechnology in the current research scenario.
From the clinical editor:
Colloidal nanocarriers provide almost endless opportunities in the area of drug delivery. While the review mainly addresses potential oncological applications, similar approaches may be applicable in other conditions with a requirement for targeted drug delivery. Technologies including quantum dots, dendrimers, integrins, monoclonal antibodies are discussed, along with US-based patents related to these methods.
The study involved magnetic microspheres of mesalamine prepared by phase separation emulsion polymerization (PSEP) method technique. Magnetic microspheres were prepared by PSEP method to target them to the colon. Three polymers namely Eudragit S 100, ethylcellulose and chitosan were used for the preparation of magnetic microspheres. Magnetite content and entrapment of mesalamine was evaluated. Eudragit S 100, ethylcellulose and chitosan were used as polymers. Fourier transform infrared spectroscopy (FTIR) spectrum of drug and polymer was taken to visualize the compatibility of drug and polymer. Scanning electron microscope (SEM) images show the uniformity and particle size of the microspheres formed. The in vitro release study was carried out in phosphate buffer pH 6.8. The various results obtained were fit into the mathematical models and the Higuchi model was found to be most suitable for the formulations. Chitosan magnetic microspheres prepared by phase separation emulsion polymerization were found to be best in all the evaluation parameters (practical yield, magnetite content, magnetic responsivity of microspheres, particle size, in vitro release studies). They contain maximum magnetite content which is the utmost feature for the magnetic microspheres. Microspheres can be targeted by the external magnetic field applied due to magnetite entrapped. Thus toxicity and reticuloendothelial clearance can be minimized.
study investigated the anticancer effect of zerumbone (ZER) and zerumbone-loaded nanostructured lipid carrier (ZER-NLC) on the human mammary gland adenocarcinoma (MDA-MB-231) cell line. The effect of ZER and ZER-NLC on MDA-MB-231 cells was determined via electron and fluorescent microscopy and flow cytometry using the Annexin V, cell cycle, and Tdt-mediated dUTP nick-end labeling assays. We demonstrated that ZER and ZER-NLC significantly suppressed the proliferation of MDA-MB-231 cells with an IC 50 of 5.96 ± 0.13 and 6.01 ± 0.11 íµí¼g/mL, respectively. ZER and ZER-NLC arrested MDA-MB-231 cell cycle at the G2/M phase. The induction of apoptosis by ZER and ZER-NLC was via the intrinsic pathway through the release of cytochrome c and activation of caspase-3 and caspase-9. The treatments also caused the downregulation of antiapoptotic Bcl-2, Bcl-xL proteins, and proliferating cell nuclear protein and upregulation of proapoptotic Bax protein. Therefore, loading of ZER into NLC did not compromise the anticancer effects of ZER on MDA-MB-231 cells. In conclusion, ZER-NLC, which increased the bioavailability of ZER, is an effective agent in the treatment of cancers.
Objective
To study magnetic microspheres of mesalamine (5-aminosalicylic acid) for colon drug delivery.
Methods
Magnetic microspheres were prepared by solvent evaporation technique for use in the application of magnetic carrier technology. An attempt was made to target mesalamine (5-aminosalicylic acid) to its site of action i.e. to colon. Eudragit S-100, ethylcellulose and chitosan were used in three different drug: polymer ratios i.e. 1:1, 1:2 and 1:3. The microspheres were characterized in terms of particle size, percentage yield, drug content, encapsulation efficiency, in vitro release pattern and ex vivo study. The microspheres were uniform in size and shape. The in vitro release profile was studied in pH 7.4 phosphate buffer medium using USP dissolution apparatus.
Results
Chitosan microspheres were found to be better retained in terms of percentage release of the drug. Thus chitosan microspheres could be better retained at their target site.
Conclusion
Flow characteristics are also better in case of chitosan magnetic microspheres. Thus reticuloendothelial clearance can be minimized and site specificity can be increased
In the present study, nanostructured lipid carriers (NLCs) were prepared and optimized for the intravenous delivery of β-Elemene (β-E). Aqueous dispersions of NLCs were successfully prepared by high-pressure homogenization method using glycerol monostearate as the solid lipid and a mixture of Maisine 35-1 and Labrafil M1944 CS as the liquid lipid. The results revealed that the morphology of the NLCs was spheroidal. The particle size, zeta potential, and entrapment efficiency (EE) for the optimized formulation were observed as 138.9 nm, −20.2 mV, and 82.11%, respectively. X-ray diffraction analysis revealed the formation of less ordered structures in the inner core of the NLC particles. Moreover, the β-E-loaded NLCs were also less irritating and less toxic compared to Elemene injection. In addition, β-E-NLCs showed a significantly higher bioavailability and anti-tumor efficacy than Elemene injection. Taken together, our data indicate that the β-E-NLCs described in this study are well-suited for the intravenous delivery of β-E.
Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine and research, as well as in other varied sciences. Due to their unique size-dependent properties, lipid nanoparticles offer the possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could be used for secondary and tertiary levels of drug targeting. Hence, solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence have attracted wide attention of researchers. This review presents a broad treatment of solid lipid nanoparticles discussing their advantages, limitations and their possible remedies. The different types of nanocarriers which were based on solid lipid like solid lipid nanoparticles, nanostructured lipid carriers, lipid drug conjugates are discussed with their structural differences. Different production methods which are suitable for large scale production and applications of solid lipid nanoparticles are described. Appropriate analytical techniques for characterization of solid lipid nanoparticles like photon correlation spectroscopy, scanning electron microscopy, differential scanning calorimetry are highlighted. Aspects of solid lipid nanoparticles route of administration and their biodistribution are also incorporated. If appropriately investigated, solid lipid nanoparticles may open new vistas in therapy of complex diseases.
Due to their positive features (e.g., increased penetration of actives, re-enforcement of the lipid barrier and increase in skin hydration), nanostructured lipid carriers (NLC) are used in many dermal formulations. These formulations require preservation, and preservatives can impair the physical stability of disperse systems. Therefore, in this study, the influence of preservatives on the physical stability of Q10-loaded NLC was investigated using 11 different preservative mixtures. Whereas for nanosuspensions, only a limited number of preservatives are known from the literature not affecting their physical stability, a surprisingly high number of seven preservatives could be identified to be suitable for the preservation of NLC dispersions. For Q10-loaded NLC, Hydrolite 5 proved to be the best preservative, as it was found surprisingly to stabilize the NLC dispersion. Based on the data, a preservative classification system is suggested and a mechanistic model describing six key parameters affecting the physical stability of NLC could be developed. As most suitable characterization method to screen for suitable preservatives, light microscopy was identified. By being a simple, fast and cost efficient method, even extensive preservative screening studies can be performed very efficiently.
SLN have been suggested for a broad range of applications, such as intravenous injection, peroral, or dermal administration. The incorporation of the drug in the core of the SLN has to be ensured for these applications, but the inclusion of drugs in SLN is poorly understood. This study is a contribution to further describe the inclusion properties of colloidal lipids and to propose incorporation mechanisms. Besides the well known methods to investigate entrapment of actives in nanoparticles such as DSC or microscopy, the present study focussed on yet a different approach. Based on the different chemical stability of retinoids in water and in a lipid phase, a method to derive information on the distribution of the drug between SLN-lipid and the water phase was established. Comparing different lipids, glyceryl behenate gave superior entrapment compared to tripalmitate, cetyl palmitate and solid paraffin. Comparing three different drugs, entrapment increased with decreasing polarity of the molecule (tretinoin < retinol < retinyl palmitate). The encapsulation efficacy was successfully enhanced by formulating SLN from mixtures of liquid and solid lipids. These particles were solid and provided better protection of the sensitive drugs than an emulsion. X-ray investigations revealed that good encapsulation correlated with a low degree of crystallinity and lattice defects. With highly ordered crystals, as in the case of cetyl palmitate, drug expulsion from the carrier was more pronounced.
The objective of this investigation was to develop nanostructured lipid carriers (NLCs) of tacrolimus by the hot homogenization technique by sonication. NLCs are commonly prepared by emulsification and lyophilization. The feasibility of fabricating tacrolimus-loaded NLCs was successfully demonstrated in this study. The developed NLCs were characterized in terms of their particle size, zeta potential, entrapment efficiency (EE) of tacrolimus, and morphology. Studies were conducted to evaluate the effectiveness of the NLCs in improving the penetration rate through hairless mouse skin. Tacrolimus-loaded NLCs were found to have an average size of , a zeta potential of , and an EE of 50%. In vitro penetration tests revealed that the tacrolimus-loaded NLCs have a penetration rate that is 1.64 times that of the commercial tacrolimus ointment, Protopic.
Response surface methodology (RSM) using the central composite rotatable design (CCRD) model was used to optimize formulations of dihydroartemisinin nanostructured lipid carrier (DHA–NLC). The CCRD consisting of three-factored factorial design with three levels was used in this study. The drug encapsulation efficiency (EE), drug loading (DL) percentage and particle size of DHA–NLC were investigated with respect to three independent variables including DHA concentration (X1), lipid concentration (X2) and ratio of liquid lipid to total lipid (X3). The result showed that the optimal formulation could be obtained from this response surface methodology. The optimal formulation for DHA–NLC was composed of DHA concentration (X1) of 1g/l, lipid concentration (X2) of 1% and ratio of liquid lipid to total lipid (X3) of 0.1:1. DHA–NLC under the optimized conditions gave rise to the EE of (98.97±2.3) %, DL of (15.61±1.9) %, mean diameter of (198±4.7) nm, polydispersity index (PI) of 0.146 and zeta potential value of (−21.6±1.3) mV. TEM of the optimized NLC showed spherical particles. The in vitro experiments proved that DHA in the NLC released gradually over the period of 48h. This study showed that the RSM–CCRD could efficiently be applied for the modeling of DHA–NLC.
Oridonin, a lipophilic Chinese medicine, has very low oral bioavailability due to its poor solubility. Solid lipid nanoparticle (SLN) delivery systems of oridonin have been formed using stearic acid, soybean lecithin and pluronic F68 in our studies to overcome this problem. Emulsion evaporation–solidification at low temperature was used to prepare SLN dispersions. The particle size and morphology were examined by transmission electron microscopy (TEM), and the zeta potential was measured by a television micro-electrophoresis apparatus. Process and formulation variables have been studied and optimized on the basis of entrapment efficiency. Differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD) studies were performed to characterize the state of the drug. In vitro release studies were performed in phosphate-buffer solution (PBS) (pH 7.4). The tissue distribution in mice and the pharmacokinetics in rabbits were studied to evaluate the tissue targeted property of SLNs. Stable SLN formulations of oridonin having a mean size range of 15–35 nm and mean zeta potential −45.07 mV were developed. More than 40% oridonin was entrapped in SLNs. DSC and PXRD analysis showed that oridonin is dispersed in SLNs in an amorphous state. The release pattern of the drug was analysed and found to follow the Higuchi equations. In vivo studies demonstrated that oridonin-loaded SLNs obviously increased the concentration of oridonin in liver, lung and spleen, while its distribution in heart and kidney decreased.
By inserting L-arginine lauril ester (AL) into nanostructure lipid carriers (NLCs) and then coating with bovine serum albumin (BSA), pH-sensitive membranolytic and lysosomolytic nanocarriers (BSA-AL-NLCs) were developed. Hemolysis assay demonstrated the pH-sensitive biomembrane disruptional capability of AL and BSA-AL-NLCs. BSA-AL-NLCs did not disrupt biomembrane at pH 7.4 even at high concentration, exhibited ideal feasibility as lysosomolytic drug delivery nanoparticles without cytotoxicity. Confocal Laser Scanning Microscope (CLSM) images confirmed the lysosomolytic capability of BSA-AL-NLCs after internalized into MCF-7 (human breast cancer cell) via endosome-lysosome path in vitro. Paclitaxel (PTX) loaded BSA-AL-NLCs displayed pH-dependent release in vitro. In MCF-7 viability test with MTT assays, both the blank NLCs did not exhibit cellular toxicity. Of particular interest, the in vitro cell experiments demonstrated that the anti-tumor effect of PTX-loaded BSA-AL-NLCs was preferable to BSA-NLCs, even comparable with PTX solution, which indicated that AL served to facilitate lysosomal escape of BSA-AL-NLCs so as to improve the anti-cancer effect. Biodistribution and anti-cancer activity in vivo confirmed the improved tumor targeting and anti-cancer efficacy of BSA-AL-NLCs. The study suggested that the simple and small molecule of AL may render more nanocarriers lysosomolytic capability with lower cytotoxicity, as well as improved therapeutic index of loaded active agents.
A drug carrier of colloidal lipid particles with improved payloads and enhanced storage stability was investigated. Based on the experiences with hard fats nanoparticles, a new type of solid lipid nanoparticles (SLN) has been developed by incorporating triglyceride containing oils in the solid core of said particle. The structure and mixing behaviour of these particles were characterised and practical implications on controlled release properties tested. Nanoparticles were characterised by their melting and recrystallisation behaviour as recorded by differential scanning calorimetry (DSC). Polymorphic form and bilayer arrangement were assigned by wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering (SAXS). Size distribution and storage stability were investigated by laser diffractometry (LD). Release properties were studied by drug release model according to Franz. A medium chain triglyceride oil was incorporated successfully in a matrix of a solid long chain glyceride. The crystal order was greatly disturbed, however, the carrier remained solid. The oil inside the particle remained in a liquid state and induced a slight shift form the β′ polymorph to the βi form. Long spacings varied within 0.1 nm with increasing oil loads. Nanoparticles with low oil concentrations showed sustained release properties. Improved drug load levels were encapsulated by lipid particles supplemented with oily constituents. Thus, the presented carrier adds additional benefits to the well-known opportunities of conventional SLN and is suited for topical use.
Nanostructured lipid carrier (NLC) systems were developed using response surface methodology to optimize the concentrations of lipophilic and hydrophilic surfactants based on the size of the resulting NLC. From preliminary experiments, a formulation composed of Precirol, Myverol, and Pluronic formed a stable NLC dispersion. Concentrations of the surfactants, Myverol and Pluronic, were optimized by a central composite design and response surface methodology. Lutein (phylloquinone) was used as a lipophilic drug in the NLC system. The particle size and polydispersion index of the NLC were measured using photon correlation spectroscopy. The ultrasonication duration and drug load were found to significantly impact the particle size of the NLCs prepared. The prepared NLCs were examined by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and transmission electron microscopy (TEM) and found to have an imperfect crystalline lattice and a spherical morphology. The lutein-loaded NLCs had high release rates of the drug in simulated intestinal fluid compared to simulated gastric fluid using modified Franz diffusion cells. Sustained-release lutein delivery was achieved using NLC technology.
Solid lipid nanoparticles (SLN) have attracted increasing attention during recent years. This paper presents an overview about the selection of the ingredients, different ways of SLN production and SLN applications. Aspects of SLN stability and possibilities of SLN stabilization by lyophilization and spray drying are discussed. Special attention is paid to the relation between drug incorporation and the complexity of SLN dispersions, which includes the presence of alternative colloidal structures (liposomes, micelles, drug nanosuspensions, mixed micelles, liquid crystals) and the physical state of the lipid (supercooled melts, different lipid modifications). Appropriate analytical methods are needed for the characterization of SLN. The use of several analytical techniques is a necessity. Alternative structures and dynamic phenomena on the molecular level have to be considered. Aspects of SLN administration and the in vivo fate of the carrier are discussed.
Triamcinolone acetonide (TA) is a corticosteroid drug currently administered by intravitreal injection for a broad spectrum of inflammatory, edematous and angiogenic ocular diseases. To increase the drug's bioavailability by ocular instillation, TA was encapsulated in nanostructured lipid carriers (NLC), previously optimized by our group using a factorial design approach. In the present paper, nanometric (∼200 nm), unimodal and negatively charged NLC loaded with the fluorescent lipid marker Nile red (NR-NLC) and drug (TA-NLC) were produced by high pressure homogenization. Based on the selected formulations, in vivo tests were carried out by eye-drop instillation of NR-NLC in mice, revealing the systems' ability of delivering lipophilic actives to the posterior segment of the eye via the corneal and non-corneal pathways. Short and long-term stability of TA-NLC was assessed by high performance stability analysis using the Turbiscan®. The results showed a backscattering of less than 1.5% and during a period of 6 months, anticipated the low tendency of these particles for aggregation during shelf life when stored at room temperature.
Due to the multiple barriers imposed by the eye against the penetration of drugs, the ocular delivery and targeting are considered difficult to achieve. A major challenge in ocular drug therapy is to improve the poor bioavailability of topically applied ophthalmic drugs by overcoming the severe constraints imposed by the eye on drug absorption. One of the promising strategies nowadays is the use of colloidal carrier systems characterized by a submicron-meter size. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives to conventional and very popular ocular carrier systems, such as the nanoemulsions, liposomes, and polymeric nanoparticles. Nevertheless, taking into account the characteristics of the eye, morphometrical properties of the colloidal systems (e.g., average particle size and polydispersion) may represent a limiting factor for topical application without induced corneal irritation, being responsible for the selected system. This review article focuses on the application of lipid nanoparticles (SLN, NLC) as carriers for both non-steroidal and steroidal anti-inflammatory drugs for the treatment of ocular inflammatory disorders. Major benefits, as well as shortcomings, of ocular inflammation conditions are described, in particular upon management of inflammation induced by ocular surgery (e.g., cataracts, refractive surgery). Particular emphasis is given to the clinical choices currently available, while examining the most recent drugs that have been approved.
Bufadienolides-loaded nanostructured lipid carriers (BU-NLC) were prepared for parenteral application using glyceryl monostearate as solid core, medium-chain triglyceride and oleic acid as liquid lipid material, and Lipoid E-80, sodium deoxycholate and pluronic F68 as stabilizers. In this study, the in vitro cytotoxicity, pharmacokinetics, biodistribution, antitumor efficacy and safety of BU-NLC were evaluated. Against human astrocytoma cell line (U87-MG) and human gastric carcinoma cell line (HGC-27) BU-NLC exhibited cytotoxicity that was similar to that of the free drug, and superior to that of the commercially available fluorouracil injection. BU-NLC exhibited a linear pharmacokinetic behavior at doses ranging from 0.25 to 1.0 mg/kg. The improved pharmacokinetic profile of bufadienolides when formulated in BU-NLC resulted in a higher plasma concentration and lower clearance after intravenous administration compared with bufadienolides solution (BU-S). A biodistribution study indicated that bufadienolides were mainly distributed in the lung, spleen, brain and kidney, and the longest retention was observed in the brain. A sarcoma-180 tumor model further confirmed the advantages of BU-NLC versus BU-S. Hemolysis and acute toxicity investigations showed that BU-NLC was safe when given by intravenous injection with reduced toxicity. In conclusion, the NLC system is a promising approach for the intravenous delivery of bufadienolides.
To investigate the possibility of reconstituted protein-free high-density lipoprotein (HDL) being a carrier for delivering a lipophilic cardiovascular drug, Tanshinone IIA-loaded HDL-like nanostructured lipid carriers (TA-NLC) were prepared by a nanoprecipitation/solvent diffusion method. The physicochemical parameters of TA-NLC were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, differential scanning calorimetry (DSC) and stability. A novel two-step method has been employed to determine entrapment efficiency of TA-NLC. The binding properties of TA-NLC to apolipoproteins were investigated by in vitro incubation competition assay in the presence of native HDL and electrophoresis test. Phagocytosis and cytotoxicity was evaluated using mouse macrophage cell line RAW 264.7 with TA-NLC and incubated TA-NLC with native HDL (TA-NLC-apo). The results showed that TA-NLC had an average diameter of 8.0+/-1.2 nm, zeta potential of -29.0+/-0.0 mV, drug loading of 6.17+/-0.3% and entrapment efficiency of 97.84+/-1.2%. TA-NLC were demonstrated spheres with drug incorporated in lipid core forming a shell-core structure. DSC analysis showed that TA was dispersed in NLC in an amorphous state. The incorporation of glycerol trioleate to NLC led to crystal order disturbance. Agarose gel electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-SPAGE) patterns indicated that TA-NLC could bind to apolipoprotein A-I (apoA-I) specifically in vitro. Phagocytosis studies showed significant differences in uptake between TA-NLC and TA-NLC-apo and demonstrated that TA-NLC incubated with native HDL could turn endogenous by association to apolipoproteins, which cannot trigger immunological responses and could escape from recognition by macrophages.
Nanostructured lipid carriers (NLC) are new drug systems composed of physiological lipid materials. The possibility of including different types of lipids into the NLC structure revealed the wide prospects for using biologically active natural oils for the development of the cutaneous preparations. In this study the formulation parameters of NLC on the basis of Siberian pine seed oil were evaluated including concentration of lipids, types of surfactants and storage conditions (4 degrees C, 20 degrees C, 40 degrees C). Size distribution and storage stability of formulations produced by hot high pressure homogenisation were investigated by laser diffractometry and photon correlation spectroscopy. The NLC were characterised by their melting behaviour using differential scanning calorimetry. The obtained data indicated the high physical stability of the developed NLC formulations.
The aim of the current study was to encapsulate celecoxib (Cxb) in the nanostructured lipid carrier (Cxb-NLC) nanoparticles and evaluate the lung disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate using high-pressure homogenization. Cxb-NLC nanoparticles were characterized for physical and aerosol properties. In-vitro cytotoxicity studies were performed with A549 cells. The lung deposition and pharmacokinetic parameters of Cxb-NLC and Cxb solution (Cxb-Soln) formulations were determined using the Inexpose system and Pari LC star jet nebulizer. The particle size and entrapment efficiency of the Cxb-NLC formulation were 217+/-20nm and >90%, respectively. The Cxb-NLC released the drug in controlled fashion, and in-vitro aerosolization of Cxb-NLC formulation showed an FPF of 75.6+/-4.6%, MMAD of 1.6+/-0.13microm and a GSD of 1.2+/-0.21. Cxb-NLC showed dose and time dependent cytotoxicity against A549 cells. Nebulization of Cxb-NLC demonstrated 4 fold higher AUC(t)/D in lung tissues compared to the Cxb-Soln. The systemic clearance of Cxb-NLC was slower (0.93l/h) compared to the Cxb-Soln (20.03l/h). Cxb encapsulated NLC were found to be stable and aerodynamic properties were within the respirable limits. Aerosolization of Cxb-NLC improved the Cxb pulmonary bioavailability compared to solution formulation which will potentially lead to better patient compliance with minimal dosing intervals.
Nanostructured lipid carriers (NLCs) made from mixtures of Precirol and squalene were prepared to investigate whether the bioavailability of lovastatin can be improved by oral delivery. The size, zeta potential, drug-loading capacity, and release properties of the NLCs were compared with those of lipid nanoparticles containing pure Precirol (solid lipid nanoparticles, SLNs) and squalene (lipid emulsions, LEs). Stable nanoparticles with a mean size range of 180-290 nm and zeta potential range of -3 to -35 mV were developed. More than 70% lovastatin was entrapped in the NLCs and LEs, which was significantly higher compared to the SLNs. The in vitro release kinetics demonstrated that lovastatin release could be reduced by up to 60% with lipid nanoparticles containing Myverol as the lipophilic emulsifier, which showed a decreasing order of NLCs>LEs>SLNs. Drug release was further decreased by soybean phosphatidylcholine (SPC) incorporation, with NLCs and SLNs showing the slowest delivery. The oral lovastatin bioavailability was enhanced from 4% to 24% and 13% when the drug was administered from NLCs containing Myverol and SPC, respectively. The in vivo real-time bioluminescence imaging indicated superior stability of the Myverol system over the SPC system in the gastric environment.
The introduction of atomic force microscopy (AFM) techniques has revolutionised our ability to characterise colloidal objects. AFM allows the visualisation of samples with sub-nanometre resolution in three dimensions in atmospheric or submerged conditions. Nanomedical research is increasingly focused on the design, characterisation and delivery of nano-sized drug carriers such as nanoparticles, liposomes and polyplexes, and this review aims to highlight the scope and advantages of AFM in this area. A significant amount of work has been carried out in drug delivery system (DDS) research in recent years using a large variety of techniques. The use of AFM has enabled us to directly observe very small objects without the need of a cumbersome and potentially contaminating sample preparation. Thus, nanoscale DDS can be investigated in a controlled environment without the necessity of staining or drying. Moreover, intermittent contact mode AFM allows the investigation of soft samples with minimal sample alteration; phase imaging allows accessing information beyond the sample's topography and also differentiating between different materials, and force spectroscopy experiments help us to understand the intrinsic structure of DDS by recording the elastic or adhesion behaviour of particles. Hence, AFM enables us accessing information which is hardly available by other experimental techniques. It has provided invaluable information about physicochemical properties and helped to shed light on the area of nanoscale drug delivery and will, with more and more sophisticated equipment becoming available, continue to add to our understanding of the behaviour of nanoscale DDS in the future.
The advent of nanotechnological products in the market, while holding great promise, is raising concerns in consumers. Therefore, this contribution will attempt to compare different particulate formulations and to answer whether their passive penetration into, and potential permeation through the skin may be possible or not. To this end, skin structure, composition, and penetration paths will be concisely reviewed. Parameters generally cited to affect skin absorption will be resumed and commented on from the perspective of potentially penetrating nanosized agents. These sections will provide the basis to understand what is fiction and what is reality.
Nifedipine (NI) is a poorly water-soluble drug and its oral bioavailability is very low. To improve the water solubility, NI-lipid nanoparticle suspensions were prepared by a combination of co-grinding by a roll mill and high-pressure homogenization without any organic solvent. The mean particle size and zeta potential of the NI-lipid nanoparticle suspensions were about 52.6 nm and -61.8 mV, respectively, and each parameter remained extremely constant during a period of 4 months under 6 degrees C and dark conditions, suggesting that the negative charge of the phospholipid, dipalmitoyl phosphatidylglycerol, is very effective in preventing coagulation of the particles. In order to assure the nano-order particle size of the suspensions in view of long-term stability, a freeze-drying technique was applied to the NI-lipid nanoparticle suspensions. The mean particle size of freeze-dried NI-lipid nanoparticles after reconstitution was significantly increased in comparison to that of the preparations before freeze-drying. It was found, however, that the addition of sugars (glucose, fructose, maltose or sucrose) to the suspensions before freeze-drying inhibited the aggregation of nanoparticles, suggesting that the long-term stability storage of freeze-dried NI-lipid nanoparticles after reconstitution would be overcome. In addition, freeze-dried nanoparticles with 100mg sugar (glucose, fructose, maltose or sucrose) showed excellent solubility (>80%), whereas without sugar, as a control, showed low solubility (<20%). It was found that negatively charged phospholipids and sugars prevent coagulation of NI nanoparticle suspensions, and reproduce the nanoparticle dispersion after reconstitution; and remarkably increase the apparent solubility of nifedipine.
This study was to develop a thiolated non-ionic surfactant, cysteine-polyethylene glycol stearate (Cys-PEG-SA), for the assembling of nanoparticulate ocular drug delivery system with mucoadhesive property. Cys-PEG-SA was synthesized in two steps reaction involving a new derivative intermediate formation of p-nitrophenylcarbonyl-PEG-SA (pNP-PEG-SA). Up to 369.43+/-25.54 mumol free thiol groups per gram of the conjugates was reached. The nanostructured lipid carrier (NLC) loaded cyclosporine A (CyA) was prepared by melt-emulsification method. The mucoadhesive NLC (Cys-NLC) was obtained by incubating NLC emulsion with Cys-PEG-SA. The mucoadhesive properties of these nanocarriers were examined by using mucin particles method. The particle size or zeta potential of the porcine mucin particles were changed with the added concentration of Cys-PEG-SA, and the disulphide bond breaker cysteine significantly reduced the adhesion of Cys-NLC to mucin particles (P<0.05), whereas PEG-SA and NLC did not alternate the properties of the mucin particles. When Cys-NLC was administered topically to the rabbit eye, the encapsulated cyclosporine was found to remain on the ocular surface in the cul-de-sac for up to 6 h, both precorneal retention time and concentration were dramatically increased (P<0.05), compared with the NLC without thiomer modification.
Unlabelled:
The eyes are among the most readily accessible organs in terms of location in the body, yet drug delivery to eye tissues is particularly problematic. Poor bioavailability of drugs from ocular dosage forms is mainly due to precorneal loss factors (e.g., tear dynamics, nonproductive absorption, transient residence time in the cul-de-sac, and relative impermeability of the corneal epithelial membrane). There is a clear need for effective topical formulations capable of promoting drug penetration and maintaining therapeutic levels with a reasonable frequency of application--a strategy that can also result in enhancement of side effects that probably would not be acceptable. Delivery of a drug via a nanotechnology-based product fulfills three main objectives: enhancement of drug permeation, controlled release, and targeting. The inflammatory response of the ocular tissues is a common side effect associated with ophthalmic surgery. Together with steroidal agents, nonsteroidal anti-inflammatory drugs are used in eye surgery. In this review we focus on microemulsions, polymeric nanoparticles, liposomes, solid lipid nanoparticles, and drug nanocrystals as formulations incorporating anti-inflammatory drugs for ophthalmic application.
From the clinical editor:
This review focuses on microemulsions, polymeric nanoparticles, liposomes, solid lipid nanoparticles, and drug nanocrystals as novel high efficiency delivery systems of anti-inflammatory drugs in ophthalmic applications.
Apomorphine is a dopamine receptor agonist for treating Parkinson's disease. However, its clinical application is limited by its instability and the need for frequent injections. The aim of the present work was to develop acoustically active perfluorocarbon nanobubbles (PNs) for encapsulation of both apomorphine HCl and base forms to circumvent these delivery problems. The PNs were prepared using coconut oil and perfluoropentane as the inner phase, which was emulsified by phospholipids and cholesterol. The morphology, size, zeta potential, and drug release of the PNs were characterized. The particle size ranged from 150 to 380 nm, with differences in the oil or perfluorocarbon ratio in the formulations. Atomic force microscopy confirmed oval- or raisin-shaped particles and a narrow size distribution of these systems (polydispersity index = 0.25-0.28). The stability experimental results indicated that PNs could protect apomorphine from degradation. Evaporation of the PNs at 37 degrees C was also limited. Apomorphine HCl and base in PNs showed retarded and sustained release profiles. Ultrasound imaging confirmed the echogenic activity of PNs developed in this study. The apomorphine HCl release by insonation at 1 MHz showed enhancements of two- to fourfold compared to the non-ultrasound group, illustrating a possible drug-targeting effect. On the contrary, apomorphine base showed a decreased release profile with ultrasound application. Apomorphine-loaded PNs showed promising stability and safety. They were successful in sustaining apomorphine delivery.
Colloidal dispersions of solid lipids are under intensive investigation as drug delivery systems. In the present study, poly(vinyl alcohol) (PVA) was tested as an alternative stabilizer for triglyceride nanoparticles. The dispersions contained 10% triglyceride (trimyristin or tristearin) and 5% PVA and were prepared by high pressure melt homogenization. The nanoparticle dispersions were investigated for their thermal behavior and storage stability with special regard to the polymorphic transitions of the triglyceride matrix, including effects of storage temperature and the incorporation of model drugs (diazepam, ubidecarenone) using photon correlation spectroscopy, differential scanning calorimetry, X-ray diffraction, and transmission electron microscopy. The release of the model drug diazepam from a selected nanoparticle dispersion was investigated with differential pulse polarography. Triglyceride nanoparticles prepared with PVA displayed an unusually high stability of the metastable alpha-modification depending on the type of triglyceride and the storage conditions. In tristearin nanoparticles, the alpha-polymorph was stable for at least 9 months at refrigerator temperature and the particles exhibited a spherical shape in electron microscopic investigations. Moreover, the alpha-form in PVA-stabilized tristearin nanoparticles seemed to be highly disordered, as it did not lead to a pronounced small-angle X-ray reflection. Storage at higher temperatures led to a transformation of the particles into the beta-modification, which usually was accompanied by an increase in particle size. Incorporation of the two model drugs did not change the crystal modification of the particle matrix to a large extent. After dilution into a large volume of release medium, a large fraction of the model drug diazepam was released immediately but there was no further release over several hours. The high stability of PVA-stabilized tristearin nanoparticles with regard to particle size and alpha-modification makes them suitable as a model for investigations on the influence of the polymorphic form (e.g., in comparison with nanoparticles in the more stable beta-modification) on pharmaceutically important parameters such as drug load and drug release.
Satisfactory electron microscopic studies were not found in the literature concerning the cellular and morphologic factors which regulate alveolar clearance. On the basis of some studies it is possible to suggest a synoptic scheme of the alveolar clearance, as follows: particles can be cleared from the alveolar lumen via the tracheobronchial tree; particles are absorbed in the alveoli by macrophages which then disappear via the tracheobronchial tree or via the lymphatics; particles can be interiorized by large alveolar epithelial cells, and they can be absorbed by small alveolar epithelial cells to be transported to the interstitium; particles can be removed from the interstitium via the pulmonary blood capillaries or via the lymphatics, and they could also be absorbed in the interstitium by interstitial connective tissue cells. These routes of removal probably do exist. A new study by means of the electron microscope was set up, using tracers such as carbon and ferritin. A critical study of the literature was made as well which led to the following synoptic scheme of alveolar clearance. Particles can get cleared from the lung alveoli by: the tracheobronchial tree with not only the mucociliary escalator but also with endocytosis and digestion by nonciliated bronchiolar epithelial cells; endocytosis and digestion by the alveolar macrophages, which leave the alveolar lumen via the airways; by the granulocytes, by phagocytosis by the large alveolar (type II) cells; by endocytosis and either digestion or transcellular transport to the interstitium by small alveolar cells; by the capillaries and micropinocytosis by the endothelial cells; by the lymphatics via endothelial junctions (main route) or by endocytosis by the endothelial cells; finally, by endocytosis by interstitial macrophages, which leave the lungs via the lymphatics. The relative importance of these clearance paths and mechanisms is dependent on the characteristics of particles to be removed. Carbon particles were cleared much more slowly than ferritin molecules. The solubility of the particles is of paramount importance. The role played by particle solubilization possibly explains the variability of the clearance response as regards different materials. Carbon particles are more slowly cleared from the alveoli, are less soluble than ferritin molecules and coagulate rather easily, forming larger and still more insoluble granules. The theory of Klosterkotter (1967) on the 'lymphatic cytotoxicity concept', meaning that cytotoxic substances are to a higher extent removed by lymphatics or are strongly lymphotropic, whereas noncytotoxic particles are not removed via the lymph vessels but mainly via the airways, is discussed; but the elective function of lymphatics in clearing only toxic substances is rejected. Lymphatics undoubtedly serve a more general and widespread role in the alveolar clearance (95 references).
Lipid micropellets prepared from glycerides and phospholipids may be a physiological drug carrier system for improving the intestinal absorption of lipophilic drugs. They can be prepared by spray-drying and spray-congealing processes. In this study, formulation and optimization parameters of spray-dried and -congealed lipid pellets in the micro- and nanometer size were investigated. The rapid evaporation of solvents from the droplets, which in turn causes a rapid solidification, influenced the crystalline structures of spray-dried glycerides. Moreover, solvents, the chain length, and the type of lipids and drugs used in the formulations of spray-dried micropellets affected the surface morphology of the micropellets. In contrast to the variations of the surface structure of spray-dried micropellets, formulated spray-congealed micropellets possessed smooth surface properties. The surface morphology and microstructure of both types of micropellets were characterized by SEM.
Solid lipid nanoparticles (SLN) as alternative intravenous colloidal drug carriers were produced by high pressure homogenisation of melted lipids (glycerolbehenate, cetylpalmitate). Their surface was modified by using hydrophilic poloxamine 908 and poloxamer 407 blockcopolymers in order to reduce the phagocytic uptake by the reticuloendothelial system (RES) after i. v. injection. The phagocytosis reducing effect of the polymers was investigated in vitro in cultures of human granulocytes, uptake was quantified by chemiluminescence. Modification of the SLN with poloxamine 908 and poloxamer 407 reduced the phagocytic uptake to appr. 8-15% compared to the phagocytosis of hydrophobic polystyrene particles. The modified SLN proved more efficient in avoiding phagocytic uptake than polystyrene particles surface-modified with these blockcopolymers (48% and 38%, respectively). Viability determinations revealed the SLN to be 10 fold less cytotoxic than polylactide nanoparticles and 100 fold less than butylcyanoacrylate particles.
Assessment of the in vitro cytotoxicity of solid lipid nanoparticles (SLNs) as a function of lipid matrix (Dynasan 114, Compritol ATO 888), and stabilizing surfactant (poloxamers, Tween 80, soya lecithin, and sodium dodecyl sulphate). Comparison with other colloidal carriers should determine their potential use in the clinic.
SLNs were produced by high pressure homogenisation. Cytotoxicity was assessed by measuring the viability of HL60 cells and human granulocytes after incubation with SLNs. Particle internalisation was quantified by chemiluminescence measurements.
The nature of the lipid had no effect on viability; distinct differences were found for the surfactants. Binding to the SLN surface reduced markedly the cytotoxic effect of the surfactants, e.g., up to a factor of 65 for poloxamer 184. The permanent HL60 cell line-differentiated from cells with granulocyte characteristics by retinoic acid treatment-yielded results identical to freshly isolated human granulocytes. In general, the SLNs showed a lower cytotoxicity compared to polyalkylcyanoacrylate and polylactic/glycolic acid (PLA/ GA) nanoparticles.
Because the results are identical when using human granulocytes, differentiated HL60 cells can be used as an easily accessible in vitro test system for i.v. injectable SLN formulations. The SLNs appear suitable as a drug carrier system for potential intravenous use due to their very low cytotoxicity in vitro.
Solid lipid nanoparticles (SLN) are particulate systems for parenteral drug administration with mean particle diameters ranging from 50 up to 1000 nm. The model drugs tetracaine, etomidate and prednisolone were incorporated (1, 5 and 10%) to study the drug load, effect of drug incorporation on the structure of the lipid matrix and the release profiles and mechanism. SLN were produced by high pressure homogenization of aqueous surfactant solutions containing the drug-loaded lipids in the melted or in the solid state (500/1500 bar, 3/10 cycles). In case of tetracaine and etomidate, high drug loadings up to 10% could be achieved when using Compritol 888 ATO and Dynasan 112 as matrix material. The melting behavior of the drug loaded particles revealed that little or no interactions between drug and lipid occurred. A burst drug release (100% release < 1 min) was observed with tetracaine and etomidate SLN, which was attributed to the large surface area of the nanoparticles and drug enrichment in the outer shell of the particles. In contrast, prednisolone loaded SLN showed a distinctly prolonged release over a monitored period of 5 weeks. Depending on the chemical nature of the lipid matrix, 83.8 and 37.1% drug were released (cholesterol and compritol, respectively). These results demonstrate the principle suitability of SLN as a prolonged release formulation for lipophilic drugs.
To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosmetics, glyceryl behenate SLN loaded with vitamin A (retinol and retinyl palmitate) and incorporated in a hydrogel and o/w-cream were tested with respect to their influence on drug penetration into porcine skin. Conventional formulations served for comparison. Excised full thickness skin was mounted in Franz diffusion cells and the formulations were applied for 6 and 24 h, respectively. Vitamin A concentrations in the skin tissue suggested a certain drug localizing effect. High retinol concentrations were found in the upper skin layers following SLN preparations, whereas the deeper regions showed only very low vitamin A levels. Because of a polymorphic transition of the lipid carrier with subsequent drug expulsion following the application to the skin, the drug localizing action appears to be limited for 6-24 h. Best results were obtained with retinol SLN incorporated in the oil-in-water (o/w) cream retarding drug expulsion. The penetration of the occlusion sensitive drug retinyl palmitate was even more influenced by SLN incorporation. Transepidermal water loss (TEWL) and the influence of drug free SLN on retinyl palmitate uptake exclude pronounced occlusive effects. Therefore enhanced retinyl palmitate uptake should derive from specific SLN effects and is not due to non-specific occlusive properties.
Uptake of polycation-DNA particles is the first step in achieving gene delivery with non-viral vehicles. One of the important characteristics determining uptake of DNA particles is their size. Here we have characterized the ability of several cell lines to internalise labelled polystyrene microspheres of different sizes. All the cell lines tested ingested 20-nm microspheres avidly. With larger microspheres (93, 220, 560 and 1010 nm) cell type as well as growth related differences were observed. Whereas some cell lines (HUVEC, ECV 304 and HNX 14C) took up microspheres up to 1010 nm even when the cells were confluent, others did not take up many microspheres larger than 93 nm (Hepa 1-6 and HepG2). In one cell line (KLN 205), uptake of 93-, 220- and 560-nm microspheres was avid in growing cells, but not detectable when they were confluent. In KLN 205 cells, a good correlation was found between the uptake of 560-nm microspheres and the uptake of a peptide-DNA polyplex formulation, when it was prepared under conditions leading to small particle sizes. Little correlation was found when the polyplex formulation was allowed to aggregate.
To investigate the potential of physiological lipids as an alternative to synthetic polymeric materials such as poly(lactide-co-glycolide), peptide-containing glyceryl tripalmitate microparticles were prepared. A modified solvent evaporation method and a melt dispersion technique without the use of organic solvent were employed. Thymocartin (TP-4), an immunomodulating tetrapeptide and insulin were chosen as model peptides and incorporated as a solid or dissolved in 100 microl aqueous solution. The resulting microparticles were characterized with respect to particle size and morphology, biocompatibility, drug content (encapsulation efficiency) and in vitro release behavior. Electron spectroscopy for chemical analysis was used to investigate the adsorption of the model peptides to the lipid matrix material. The modified solvent evaporation as well as the melt dispersion method were suitable for the preparation of microparticles in the size range of 20-150 microm with an acceptable yield. The biocompatibility of the glyceryl tripalmitate microparticles after implantation into NMRI-mice was comparable to poly(lactide-co-glycolide) microparticles. The encapsulation efficiency for both model peptides was high (>80%) even at high theoretical loadings when the peptide was incorporated as a solution with the melt dispersion technique. The in vitro release behavior was substantially influenced by the physicochemical properties of the model peptides used in this study.
The suitability of cationically modified solid-lipid nanoparticles (SLN) as a novel transfection agent was investigated. SLN were produced by hot homogenisation using either Compritol ATO 888 or paraffin as matrix lipid, a mixture of Tween 80 and Span 85 as tenside and either EQ1 (N,N-di-(beta-steaorylethyl)-N,N-dimethylammonium chloride) or cetylpyridinium chloride as charge carrier. The resulting particles were approximately 100 nm in size and showed zeta potentials around +40 mV at pH 7.4. DNA binding was tested by agarose gel electrophoresis. The resulting SLN-DNA complexes were further characterised by AFM and zeta potential measurements. Only the SLN batch SII-13, composed of 4% Compritol, 4% Tween/Span and 1% EQ1, was able to form stable complexes with DNA. Typical complexes were 300 to 800 nm in size. Cytotoxicity and transfection efficiency was tested in vitro on Cos-1 cells. Cationic SLN produced by modification with EQ1 were well tolerated, with LD50 values >3 mg/ml in the LDH release assay and >0.6 mg/ml in the WST-1 assay. Further, SLN-DNA complexes containing between 10 and 200 weight equivalents of SII-13 (matrix lipid) efficiently transfected the galactosidase expression plasmid pCMVbeta in the absence and presence of the endosomolytic agent chloroquine.
The aim of this study was the comparison of two different formulations (solid lipid nanoparticles (SLN) and conventional o/w emulsion) as carrier systems for the molecular sunscreen oxybenzone. The influence of the carrier on the rate of release was studied in vitro with a membrane-free model. The release rate could be decreased by up to 50% with the SLN formulation. Further in vitro measurements with static Franz diffusion cells were performed. In vivo, penetration of oxybenzone into stratum corneum on the forearm was investigated by the tape stripping method. It was shown that the rate of release is strongly dependent upon the formulation and could be decreased by 30-60% in SLN formulations. In all test models, oxybenzone was released and penetrated into human skin more quickly and to a greater extent from the emulsions. The rate of release also depends upon the total concentration of oxybenzone in the formulation. In vitro-in vivo correlations could be made qualitatively.
The aim of this study was the investigation of the correlation between the degree of crystallinity of solid lipid nanoparticle (SLN) dispersions and their occlusive effects. SLN dispersions with different crystallinity indices of the lipid matrix were produced, physicochemically characterized and their occlusion factor was determined after 6, 24 and 48 h. This study is based on the in vitro occlusion test by de Vringer. It could be shown that the occlusion factor depends strongly on the degree of crystallinity of the lipid matrix, i.e. this effect is proportional. Further, it could be shown that noncrystalline lipid nanoparticles, i.e. supercooled melts have no occlusive properties. Therefore, the desired degree of occlusivity can be achieved by choosing suitable lipids for the matrices of topical SLN formulations.
At the beginning of the nineties solid lipid nanoparticles (SLN) have been introduced as a novel nanoparticulate delivery system produced from solid lipids. Potential problems associated with SLN such as limited drug loading capacity, adjustment of drug release profile and potential drug expulsion during storage are avoided or minimised by the new generation, the nanostructured lipid carriers (NLC). NLC are produced by mixing solid lipids with spatially incompatible lipids leading to special structures of the lipid matrix, i.e. three types of NLC: (I) the imperfect structured type, (II) the structureless type and (III) the multiple type. A special preparation process-applicable to NLC but also SLN-allows the production of highly concentrated particle dispersions (>30-95%). Potential applications as drug delivery system are described.
Lipid nanoparticles (LNP) can be prepared by rapidly injecting a solution of solid lipids in water-miscible solvents or a water-miscible solvent mixture into water. The aim of the present study was to evaluate the potential of this method for the preparation of LNP and the physicochemical characterization of the particles produced by this method. The results show that solvent injection is a potent and versatile approach for LNP preparation. Acetone, ethanol, isopropanol and methanol are suitable solvents in contrast to ethylacetate with which no LNP could be prepared. The obtained particle sizes (z-average) were between 80 and 300 nm depending on the preparation conditions. Up to 96.5% of the employed lipid was directly transformed into LNP. The LNP formation process seems to be diffusion controlled. Physicochemical characterization of the particles by differential scanning calorimetry (DSC), transmission electron microscopy and X-ray diffraction analysis reveals a distinct decrease in crystallinity of the colloidal lipid in comparison to the bulk lipid. Furthermore, DSC analysis of LNP hints at a delayed recrystallization of the colloidal lipid and the presence of two modifications. Therefore, a certain physical instability of the LNP has to be considered.
A preparation method for nanoparticles based on the emulsification of a butyl lactate or benzyl alcohol solution of a solid lipid in an aqueous solution of different emulsifiers, followed by dilution of the emulsion with water, was used to prepare glyceryl monostearate nanodispersions with narrow size distribution. To increase the lipid load the process was conducted at 47+/-2 degrees C and in order to reach submicron size a high-shear homogenizer was used. Particle size of the solid lipid nanoparticles (SLN) was affected by using different emulsifiers and different lipid loads. By using lecithin and taurodeoxycholic acid sodium salt, on increasing the GMS percentage from 2.5 to 10% an increase of the mean diameter from 205 to 695 nm and from 320 to 368nm was observed for the SLN prepared using benzyl alcohol and butyl lactate, respectively. Transmission electron micrographs of SLN reveal nanospheres with a smooth surface.
The structure of loaded solid lipid nanoparticles (SLN) has been studied to elucidate the incorporation of coenzyme Q10.
Solid-state nuclear magnetic resonance (NMR) has been applied as the principal analytical approach. In order to characterize the integration of the active ingredient coenzyme Q10 inside the solid lipid matrix, measurements of the spin-lattice relaxation time in the rotating frame have been performed.
A pattern of spin diffusion between protons of the lipid and protons of the coenzyme Q10 has been observed, which indicates two different fractions of the active ingredient: whereas the majority (60%) of the coenzyme Q10 is found to be homogeneously mixed with the solid lipid, the residual amount of 40% clearly forms a separate, solid phase associated to the particles.
A large portion of the active ingredient has been integrated homogeneously. Another, smaller fraction forms separate domains on the nanometer scale.
Tocols represent a family of tocopherols, tocotrienols, and their derivatives, and are fundamentally derived from the simplest tocopherol, 6-hydroxy-2-methyl-2-phytylchroman, which is referred to as "tocol". The most common tocol is D-alpha-tocopherol, also known as vitamin E. Tocols can be excellent solvents for water insoluble drugs and are compatible with other cosolvents, oils and surfactants. This review highlights the major developments in the use of tocols in parenteral emulsions for drug delivery, with a focus on drug solubilization, physicochemical properties, and biopharmaceutical applications. Tocol emulsions offer an appealing alternative for the parenteral administration of poorly soluble drugs, including major chemotherapeutics such as paclitaxel. Data will be presented on solubilization of paclitaxel, a key chemotherapeutic agent, and its corresponding formulation development, toxicity, efficacy and pharmacokinetic studies in animal models and humans. The breadth of the utility of tocol-based emulsions will be discussed and examples of specific therapeutic drugs and applications will be provided. As these formulations progress further in the clinic, the therapeutic utility of tocol emulsions is anticipated to expand.
The study aimed to produce solid lipid insulin-loaded micro-particles by the solvent-in-water emulsion-diffusion technique, using isobutyric acid as solvent phase, glyceryl monostearate or cetyl palmitate as lipid, soya lecithin and taurodeoxycholate as emulsifiers. Isobutyric acid, a partially water-miscible solvent with low toxicity, was used due to its high insulin-solubilization capacity. Solid lipid micro-particles of spherical shape were prepared by simple dilution of the emulsion with water. To increase the lipid load the process was conducted at 50 degrees C, and in order to reach sub-micron size, a high-shear homogeniser was used. Insulin encapsulation efficiency was about 80%. Analysis of microsphere content after processing showed that insulin did not undergo any chemical modification within the micro-particles. The in vitro release of insulin from the micro-particles was very low, and an initial burst effect of 20% of the dose was observed. After treatment of the solid lipid micro-particles with pepsin solution, an insulin loss of about 24% of the total englobed insulin was observed. The solid lipid micro-particles appear to have interesting possibilities as delivery systems for oral administration of insulin.
Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are interesting nanoparticulate delivery systems produced from solid lipids. Both carrier types are submicron size particles but they can be distinguished by their inner structure. In the present paper, indomethacin (IND)-loaded SLN and NLC were prepared and the organization and distribution of the different ingredients originating each type of nanoparticle system were studied by differential scanning calorimetry (DSC) technique. Furthermore, mean particle size and percentage of drug encapsulation were also determined. From the results obtained, NLC lipid organization guaranteed an increased indomethacin encapsulation in comparison with SLN. DSC static and dynamic measurements performed on SLN and NLC showed that oil nanocompartments incorporated into NLC solid matrix drastically influenced drug distribution inside the nanoparticle system. Controlled release from NLC system could be explained considering both drug partition between oil nanocompartments and solid lipid and a successive partition between solid lipid and water.