No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Antioxidant activity of quercetin in Eudragit-coated liposomes for intestinal delivery
Abstract
Quercetin, a natural polyphenol with strong antioxidant activity, was loaded in Eudragit-coated liposomes conceived for intestinal delivery. Eudragit was used to form a protective shell on the surface of liposomes to resist gastric environment and allow the delivery of quercetin to the intestine. The physico-chemical properties of the liposomes were assessed by light scattering and cryogenic transmission electron microscopy. Small, spherical, uni- and bilamellar liposomes were produced, with the presence of multilamellar structures in Eudragit-coated liposomes. The Eudragit coating increased the physical stability of the vesicular system in fluids mimicking the gastrointestinal environment. Further, the incorporation of quercetin in the vesicular system did not affect its intrinsic antioxidant activity, as DPPH radical was almost completely inhibited, and the vesicles were also capable of ensuring optimal protection against oxidative stress in human intestinal cells by reducing reactive oxygen species (ROS)production. The proposed approach based on quercetin vesicular formulations may be of value in the treatment of pathological conditions associated with intestinal oxidative stress.
... It is found in many fruits and vegetables, and, among vegetables, the highest levels of QUE have been found in onions (Allium cepa L.), red leaf lettuce (Lactuca sativa L.), and asparagus (Asparagus officinalis L.), while lower levels in broccoli, green peppers, peas, and tomatoes (Manconi et al., 2020;Di Petrillo et al., 2022). QUE supplementation may promote antioxidant, antiinflammatory, immunoprotective effects, anticarcinogenic, and antidiabetic activities, and can prevent many chronic diseases, added to the ability to inhibit lipid peroxidation, platelet aggregation, capillary permeability, and to stimulate mitochondrial biogenesis (Caddeo et al., 2019;Di Petrillo et al., 2022). Due to its biocompatibility and pharmaceutical properties, QUE is increasingly being used in new formulations for different treatments (Di Petrillo et al., 2022). ...
... The results suggest that the prepared succinyl-chitosan liposomes are effective delivery systems for the incorporation, protection, and release of bioactive polyphenols intended for oral administration (Caddeo et al., 2017). Subsequently, the same authors, developed Eudragit-coated liposomes for the delivery of QUE (Caddeo et al., 2019). Eudragit increased the physical stability of the vesicular system in fluids that mimicked the gastrointestinal environment. ...
... Eudragit increased the physical stability of the vesicular system in fluids that mimicked the gastrointestinal environment. Furthermore, the incorporation of QUE into the vesicular system did not affect its intrinsic antioxidant activity, as the 2,2-diphenyl-1-picrylhydrazyl radical was almost completely inhibited and the vesicles were able to guarantee optimal protection against oxidative stress in vesicles human intestinal cells, reducing the production of ROS (Caddeo et al., 2019). Furthermore, the authors underscore the importance of exploring the combination of polyphenols for the treatment of intestinal conditions associated with inflammation and oxidative stress (Caddeo et al., 2016(Caddeo et al., , 2017(Caddeo et al., , 2019. ...
Inflammatory bowel disease (IBD) is commonly known to be classified into two major subtypes, namely ulcerative colitis (UC) and Crohn’s disease (CD). Currently, nonsteroidal antiinflammatory drugs, glucocorticoids, and immunosuppressive agents are used for the treatment of IBD, while their clinical application is severely limited due to unwanted side effects. The investigation of natural bioactive for the treatment of IBD due to the potent antiinflammatory pharmacological efficacy has become an alternative. In recent years, in vitro and in vivo experiments have shown that encapsulation of these bioactive in drug delivery systems (DDSs) can improve solubility, stability, bioaccessibility, bioavailability, and targeting capability. Our focus in this chapter was to highlight the use of natural bioactive compounds (especially of plant origin) encapsulated in delivery systems based on synthetic polymers, natural polymers (derived from polysaccharides and proteins), and lipids for the treatment of IBD.
... As expected, QCN efficiently decreased the level of DPPH free radical and exhibited a strong anti-oxidant effect as observed in previous studies, whereas TA displayed a minimal anti-oxidant effect (Hatahet et al., 2017;Caddeo et al., 2019). A higher concentration of QCN (20 µM) demonstrated an enhanced antioxidant effect compared to 15 µM by significantly inhibiting DPPH by 67% (p < 0.05). ...
Age-related macular degeneration (AMD) is a multifactorial degenerative disease characterised by the gradual loss of central vision in individuals aged more than 50 years. There is currently no cure for this disease, but treatment can delay its progression. Consequently, there is an urgent need for the development of both new and cost-effective therapeutics. In this study, a novel combination of a corticosteroid and flavonoid was investigated on human retinal pigment epithelial cell lines to explore its potential pharmacological effect on AMD. Combination therapies, such as anti-VEGF (vascular endothelial growth factor) agents combined with photodynamic therapy and anti-VEGF agents in conjunction with corticosteroids, have been utilized previously and are known to be effective. However anti-VEGF injections are associated with serious side effects and are costly. Various disease conditions associated with AMD were stimulated on human retinal cells, which were then exposed to different concentrations of triamcinolone acetonide (TA) and quercetin (QCN) individually and in combination. This investigation aimed to assess their potential for the treatment of AMD. The combination of TA and QCN demonstrated a superior anti-inflammatory effect, as TA and QCN primarily act on different inflammatory signaling pathways. Furthermore, in terms of anti-VEGF activity, both drugs exert their effects through different mechanisms: QCN inhibits kinase pathways leading to the deactivation of VEGF receptors, whereas TA destabilises VEGF mRNA, resulting in increased suppression of VEGF-C with combination treatments. The anti-oxidant assay yielded similar outcomes, demonstrating a synergetic effect when treated with combination drugs. These findings collectively suggest TA and QCN as a promising combination therapy for targeting AMD with multiple pathological conditions.
... Encapsulation of QU in nanocarriers effectively improves the bioavailability of QU and allows for better efficacy [16]. For example, encapsulated QU in Eudragit-coated liposome was designed for intestinal delivery to resist the gastric acid environment [21]. The use of QU-loaded liposomes in a rat model of ischemia-reperfusion resulted in a substantial downregulation of all pro-inflammatory markers [22]. ...
Neurodegenerative diseases (NDDs) are mainly induced by oxidative stress which produces excessive reactive oxygen species (ROS). Quercetin (QU) is a potent antioxidant with some effects on NDDs. This study prepared and characterized a novel glucose-modified QU liposome (QU–Glu–Lip), aiming not only to overcome QU’s poor water solubility and bioavailability but also to deliver more QU to brain tissue to enhance its neuroprotective effect. QU–Glu–Lip possessed encapsulation efficiency (EE) of 89.9%, homogenous particle sizes (116–124 nm), small PDI value (<0.3), zeta value −1.363 ± 0.437 mV, proper pH and salt stability, and proper cytotoxicity. The glucose-modified liposome penetrated the blood–brain barrier (BBB) mediated via the glucose transporter 1 (GLUT1) and was taken by neuronal cells more efficiently than liposome without glucose, according to bEnd.3 and PC12 cell tests. QU–Glu–Lip attenuated H2O2-induced oxidative damage to PC12 with higher cell viability (88.42%) and lower intracellular ROS compared to that of QU. QU–Glu–Lip had higher brain target ability and delivered more QU to neuronal cells, effectively exerting the antioxidative neuroprotection effect. There is potential for the QU–Glu–Lip application for more effective treatment of NDDs.
... Such formulations solubilize the molecule via hydrophobic interaction in their non-polar regions [9]. Additionally, these can be protected against degradation in gastric fluid by coating with pH-sensitive excipients [10,11]. Nevertheless, the risks related to dilution-induced dissociation and premature leakage of the payload and poor dispersion stability of self-assembled formulations cannot be eliminated. ...
Objective:
The aim of this study is to demonstrate the effect of stoichiometry upon characteristics of quercetin-arginine (QCT-Arg) cocrystals.
Significance:
Quercetin (QCT) is a most abundant flavonoid in vegetables and fruits and has been widely used as an antioxidant. However, its oral bioavailability remains low due to poor aqueous solubility. We illustrate that QCT-Arg cocrystals formulated through an optimized stoichiometry can be a useful approach for its solubilization.
Method:
Cocrystals were prepared using solvent evaporation method. Characterizations were performed through microscopic, spectroscopic, and thermal techniques. The stoichiometry was confirmed from the binary phase diagram which was prepared using thermograms derived from differential scanning calorimetric experiments.
Result:
Cocrystal formation was accompanied by the conversion of isotropic phase into anisotropic one. Thread-like cocrystals were formed, regardless of QCT-Arg stoichiometry and solvent's polarity. Spectral analyses suggested that cocrystal structure was held together by hydrogen bonding between QCT and Arg. We ruled out the existence of eutectic mixture based on the observation of two eutectic points in the binary phase diagram.
Conclusion:
Morphology of cocrystals remained unaffected by the solvent type, stoichiometry and the presence of surfactant. We noticed that the cocrystals could improve the aqueous solubility of QCT.
... Antioxidant compounds possess the ability to counteract the DPPH radical via two distinct mechanisms: either radical quenching aided by hydrogen atom donation or direct reduction aided by electron donation. Each sample's ability to scavenge DPPH radicals was evaluated as a percentage of antioxidant activity using the formula below [63]. The agar well diffusion technique was used to examine the HSD-loaded transethosome's antibacterial efficacy. ...
In this study, hesperidin was loaded into a transethosome and was developed employing the rotary evaporator method. The formulation was optimized using the Box–Behnken design (BBD). The optimized HSD-TE formulation has a spherical shape, vesicle size, polydispersity index, entrapment efficiency, and zeta potential within the range of 178.98 nm; the PDI was 0.259 with a zeta potential of −31.14 mV and % EE of 89.51%, respectively. The in vitro drug release shows that HSD-TE exhibited the release of 81.124 ± 3.45% in comparison to HSD suspension. The ex vivo skin permeation showed a 2-fold increase in HSD-TE gel permeation. The antioxidant activity of HSD-TE was found to be 79.20 ± 1.77% higher than that of the HSD solution. The formulation showed 2-fold deeper HSD-TE penetration across excised rat skin membranes in confocal laser microscopy scanning, indicating promising in vivo prospects. In a dermatokinetic study, HSD-TE gel was compared to HSD conventional gel where TE significantly boosted HSD transport in the epidermis and dermal layers. The formulation showed greater efficacy than free HSD in the inhibition of microbial growth, as evidenced by antibacterial activity on the Gram-negative and positive bacteria. These investigations found that the HSD-TE formulation could enhance the topical application in the management of cutaneous bacterial infections.
... As a result, the suggested formulation can control inflammatory and oxidative circumstances that can lead to DNA damage and cell alterations. [100] A simple electrostatic deposition method was developed to encapsulate quercetin within chitosan/ lecithin polymeric nano-capsules, preventing it from degrading and increasing its biocompatibility. Size, shape, encapsulation efficiency, antioxidant effect, storage stability, and antiproliferative effects of quercetin-encumbered polymeric nano-capsules (Q-NPs) were studied. ...
The target delivery of sensitive components to get the intended benefits is a challenge for the global food industry. One of the principal strategies used to boost individualized absorptivity, nutrient stability, and enhanced food quality is the application of liposomal systems in the food industry, which allows controlled release of bioactive compounds. Lipid-oriented encapsulation strategies such as liposomes are superior for encapsulating sensitive components, increasing product solubility and bioavailability, and accurately targeting encapsulated content in food and nutraceutical production. In this review, the nature, composition, and different methodologies for the preparation of liposomes, such as the Bangham Method, ethanol injection method, microfluidic channel method, and freeze-drying method summarized. Moreover, the crucial role of liposomes in delivering sensitive bioactive compounds to cure different health maladies has been emphasized.
... A variety of structures from small, spherical, uni-, and bi-lamellar to multi-lamellar liposomes were observed. The human intestinal cells were highly protected against oxidative stress by lowering the generation of reactive oxygen species and incorporating quercetin into the vesicles [8]. ...
The aim of the present study is the development, physicochemical characterization, and in vitro cytotoxicity evaluation of both empty and quercetin-loaded HSPC (hydrogenated soy phosphatidylcholine) liposomes, GMO (glyceryl monooleate) liquid crystalline nanoparticles, and PHYT (phytantriol) liquid crystalline nanoparticles. Specifically, HSPC phospholipids were mixed with different non-ionic surfactant molecules (Tween 80 and/or Span 80) for liposomal formulations, whereas both GMO and PHYT lipids were mixed with Span 80 and Tween 80 as alternative stabilizers, as well as with Poloxamer P407 in different ratios for liquid crystalline formulations. Subsequently, their physicochemical properties, such as size, size distribution, and ζ-potential were assessed by the dynamic and electrophoretic light scattering (DLS/ELS) techniques in both aqueous and biological medium with serum proteins. The in vitro biological evaluation of the empty nanosystems was performed by using the MTT cell viability and proliferation assay. Finally, the entrapment efficiency of quercetin was calculated and the differences between the two different categories of lipidic nanoparticles were highlighted. According to the results, the incorporation of the non-ionic surfactants yields a successful stabilization and physicochemical stability of both liposomal and liquid crystalline nanoparticles. Moreover, in combination with an appropriate biosafety in vitro profile, increased encapsulation efficiency of quercetin was achieved. Overall, the addition of surfactants improved the nanosystem’s stealth properties. In conclusion, the results indicate that the physicochemical properties were strictly affected by the formulation parameters, such as the type of surfactant.
... Hydrophobic compounds (like quercetin) can be enclosed inside the non-polar sections of the phospholipid bilayers, whereas hydrophilic molecules (like water) can be encased within the watery core [187]. The potential of liposomes to enhance the bioactivity and bioavailability of quercetin has been the subject of several investigations [188][189][190]. It has been demonstrated that liposomes offer defense against the stomach's enzymes and acids [191]. ...
Quercetin, a flavonoid found in fruits and vegetables, has been a part of human diets for centuries. Its numerous health benefits, including antioxidant, antimicrobial, anti-inflammatory, antiviral, and anticancer properties, have been extensively studied. Its strong antioxidant properties enable it to scavenge free radicals, reduce oxidative stress, and protect against cellular damage. Quercetin’s anti-inflammatory properties involve inhibiting the production of inflammatory cytokines and enzymes, making it a potential therapeutic agent for various inflammatory conditions. It also exhibits anticancer effects by inhibiting cancer cell proliferation and inducing apoptosis. Finally, quercetin has cardiovascular benefits such as lowering blood pressure, reducing cholesterol levels, and improving endothelial function, making it a promising candidate for preventing and treating cardiovascular diseases. This review provides an overview of the chemical structure, biological activities, and bioavailability of quercetin, as well as the different delivery systems available for quercetin. Incorporating quercetin-rich foods into the diet or taking quercetin supplements may be beneficial for maintaining good health and preventing chronic diseases. As research progresses, the future perspectives of quercetin appear promising, with potential applications in nutraceuticals, pharmaceuticals, and functional foods to promote overall well-being and disease prevention. However, further studies are needed to elucidate its mechanisms of action, optimize its bioavailability, and assess its long-term safety for widespread utilization.
... The variables evaluated in this study were the following ( Table 1): variation of the volume of OP over AP and constant polymer amount (PA) (12 mL + 50 mg, respectively), a variation of the volume of AP over OP and constant PA (12 mL + 50 mg, respectively), and variation of the PA over constant OP and AP volumes (12 mL each). The amounts tested were as follows: for OP and AP, the volumes of 5,8,10,12,15,18, and 20 mL; for PA, the amounts of 5, 10, 25, 50, 75, and 100 mg of each polymer. The nano-emulsions were homogenized as previously described. ...
Eudragit® polymers have proven their potential as a means to control the release of aqueous insoluble drugs in various delivery systems as polymer nanoparticles (PNPs). The size (S) and polydispersity index (PDI) of PNPs are crucial factors for their interaction with biological systems from a pharmaceutical standpoint. This study aimed to determine the impact of the volumes of the organic phase (OP) and aqueous phase (AP), as well as the polymer amount (PA), on the size and PDI of PNPs prepared using the nanoprecipitation method for encapsulating quercetin (Qr). The study also evaluated the toxic effects of PNPs on human erythrocytes. The PNPs were prepared using preformed polymers derived from methacrylic acid and polyvinyl alcohol (PVA) as a surfactant. The nanoprecipitation technique enabled the production of particles smaller than 200 nm with a PDI lower than 0.2, and the study established the significant impact (p < 0.05) of the three variables related to the polymers and solvents. The selected PNPs contained 5 mg of Qr and 50 mg of Eudragit polymers (1:10 w/w Eudragit® EPO, E100, L100, and Eudragit L100-55) and diverse concentrations of PVA. The study found that including PVA in the AP increased the Qr encapsulation by up to 98%. The hemolytic potential of Eudragit® PNPs and Qr was assessed in human erythrocytes, with no significant cytotoxic activity observed (p < 0.001) compared with the control. In conclusion, via the nanoprecipitation technique, preparing PNPs with defined and homogeneous S to entrap the flavonol Qr efficiently is possible.
... Additionally, the biological stability of the liposomes in fluids mimicking the gastrointestinal environment was enhanced by the Eudragit coating. By lowering the generation of reactive oxygen species and incorporating QUE into the vesicles, the human intestinal cells received the highest protection against oxidative stress [77]. ...
Quercetin (QUE) is a flavonol that has recently received great attention from the research com-munity due to its important pharmacological properties. However, QUE’s low solubility and ex-tended first-pass metabolism limit its oral administration. This review aims to present the potential of various nanoformulations in the development of QUE dosage forms for bioavailability en-hancement. Advanced drug delivery nanosystems can be used for more efficient encapsulation, targeting, and controlled release of QUE. An overview of the primary nanosystem categories, formulation processes, and characterization techniques are described. In particular, lipid-based nanocarriers, such as liposomes, nanostructured-lipid carries, and solid-lipid nanoparticles, are widely used to improve QUE’s oral absorption and targeting, increase its antioxidant activity, and ensure sustained release. Moreover, polymer-based nanocarriers exhibit unique properties for the improvement of the Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADME(T)) profile. Namely, micelles and hydrogels composed of natural or synthetic polymers have been ap-plied in QUE formulations. Furthermore, cyclodextrin, niosomes, and nanoemulsions are proposed as formulation alternatives for administration via different routes. This comprehensive review provides insight into the role of advanced drug delivery nanosystems for the formulation and de-livery of QUE.
... Therefore, the proposed formulation was capable to regulate oxidative and inflammatory conditions that can cause cell modifications and damage of DNA. [1] Application of liposomes in functional foods is limited due to the same mentioned limitations, a study by Huang et al., 2020, created liposome-containing chitosan hydrogel beads with quercetin and linseed oil added. A combination of liposomes and chitosan hydrochloride solution was injected into a sodium tripolyphosphate solution to create the hydrogel beads. ...
Quercetin is a flavonoid with strong antioxidant activity considered as a potential drug candidate for number of chronic diseases; crude quercetin suffers from poor water solubility and consequently topical inactivity. Therefore, quercetin formulation within a suitable system that overcomes its solubility limitation is a matter of investigation. Many approaches were tested to improve quercetin delivery to skin. One effective approach is lipid nanocapsules. These nanoformulations are ideal in terms of average particle size and homogeneity (PDI). Hence, lipid nanoparticles are an attractive candidate for the encapsulation of quercetin for potent and effective drug delivery.
... The stability and bioavailability of labile food bioactives/nutraceuticals have been improved using several micro/nano-carriers (Caddeo et al., 2019). Because food-grade delivery vehicles are renewable, biodegradable, and biocompatible, they have been recognised as a viable platform for delivering sensitive bioactives (Rehman et al., 2020). ...
Background:
Microfluidics (MFs) and nanofluidics (NFs) techniques are emerging novel technologies gaining more attention in recent years to encapsulate bioactive compounds (bioactives) in the food, drug, and biomedical industries.
Scope and approach:
Bioactives, such as fish oil, ascorbic acid, anthocyanins, and essential oils, positively impact human health; they are often poorly absorbed and thermally unstable. In this regard, using MFs/NFs has several benefits for bioactives, e.g. improving the biostability or bioavailability and solubility by the increasing of surface area, uniform size, shape, and controlled release of them, along with their protection against degradation conditions associated with food processing and storage, as well as to ensure safe delivery to the target sites in our body. Additionally, the controlled release approach is an effective tool for delivering bioactives.
Key findings and conclusions:
Application of MFs/NFs in food processing and encapsulation of bioactives, nutraceuticals, and food additives is limited. More studies are required to establish the potential efficacy of MFs/NFs in this field. Therefore, the present review highlights various MFs techniques, including modern devices, advantages and disadvantages, the possibility of scaling up the technology, and future indications for encapsulating bioactives.
... It was shown that this compound as part of the liposomal drug Lipoflavon exhibits pronounced cardioprotective, antioxidant, angioprotective, and anti-inflammatory activity [47]. A significant antioxidant effect of quercetin was also observed in EUDRAGIT ® , a liposomal drug of polymeric composition [57]. The polymer coating of liposomes provided quercetin stability in fluids, mimicking the gastrointestinal environment, and the optimal protection of human intestinal cells from oxidative stress owing to the reduced production of reactive oxygen species (ROS). ...
This review is devoted to modern systems of nanocarriers that ensure the targeted delivery of flavonoids to various organs and systems. Flavonoids have wide range of effects on the human body due to their antioxidant, anti-inflammatory, antitumor, antimicrobial, antiplatelet and other types of activity. However, the low bioavailability of flavonoids significantly limits their practical application. To overcome this disadvantage, serious efforts have been made in recent years to develop nanoscale carriers for flavonoids. This is particularly important in view of the known antitumor effect of these compounds, which allows them to target tumor cells without affecting surrounding healthy tissues. Nanocarriers provide increased penetration of biologicals into specific organs in combination with controlled and prolonged release, which markedly improves their effectiveness. This review summarizes data on the use of phytosomes, lipid-based nanoparticles, as well as polymeric and inorganic nanoparticles; their advantages and drawbacks are analyzed; the prospect of their use is discussed that opens new possibilities for the clinical application of flavonoids.
... Various studies have proved the potent therapeutic potential of quercetin and its derivativesdue to their anti-inflammatory [7], antineoplastic [8], antioxidant [9,10], neuroprotective [7], antiallergic [11], and antimicrobial activities [12]. Due to these health- ...
Green coffee (Coffee arabica and Coffee robusta) is one of the most commonly traded goods globally. Their beans are enriched with polyphenols and numerous health benefits are associated with their consumption. The main aim of this work was to develop a new and fast analytical HPLC-MS/MS method to simultaneously determine six flavonoid polyphenolic compounds (quercetin, rutin, isorhamnetin, quercetin-3-glucouronide, hyperoside, and quercitrin) in 22 green coffee samples from six different geographical origins (Ethiopia, Brazil, Guatemala, Nicaragua, India and Colombia). In addition, by adjusting pH, temperature, solvent type, and extraction duration, several extraction methods such as acidic and alkaline hydrolysis, and extraction without hydrolysis were evaluated. The optimal extraction procedure in terms of recovery percentages (78.67–94.09%)was acidic hydrolysis at pH 2, extraction temperature of 60 °C, extraction solvent of 70% ethanol, and extraction duration of 1.5 h. Hyperoside (878–75 μg/kg) was the most abundant compound followed by quercitrin (408–38 μg/kg), quercetin (300–36 μg/kg), rutin (238–21 μg/kg), and quercetin-3-glucouronide (225–7 μg/kg), while isorhamnetin (34–3 μg/kg) showed the lowest amount. Overall, green coffee beans are rich in flavonoid polyphenolic compounds and could be used as part of a healthy diet.
... It is also commonly known as a polyphenolic flavonoid which can be found in several edible plant that are consumed on a daily diet. As an antioxidant, it can strengthen the membrane's resistance to oxidative damage caused by free radicals (4,5). Certain commercial products containing quercetin are used as dietary supplements to promote human health. ...
Introduction: Quercetin is a flavonoid found in a variety of plants, including guava, apples, onions, and tea. It’s been used as an anti-oxidant and anti-inflammatory substance for a long time. This study aims to investigate the effect of quercetin on periodontitis caused by Porphyromonas gingivalis-adhered ligatures. Methods: Eighteen male adult Sprague Dawley rats were divided into 3 groups, namely the control group (C, n=6) and the other two groups that received quercetin at 45mg/kg/day as a preventive (Qp, n=6) and a curative treatment (Qc, n=6), respectively. Under general anaesthesia, periodontitis was induced by placing a 3/0 non-resorbable sterile silk thread around the mandibular incisor teeth of eighteen male adult Sprague Dawley rats. The ligature placement caused severe irritation in the periodontal tissue. The animals were euthanized after 14 days of post-induction treatment, and samples of the mandibular portion were kept in formalin and prepared for histological processing to determine the grade of inflammation (GI). The periodontal pocket depth (PPD) was measured using the Michigan-O probe with Williams marks at the mesial and lingual sites of the rat’s incisors tooth to determine the clinical parameter. Results: Qp showed the best improvement, in both parameters, clinically (PPD score, p=0,0018 at the lingual site, and p=0,0264 at the mesial site) and histologically (GI, p=0,0002). Significant differences were found in preventing clinical attachment-loss statistically (p<0,05) on Qp, better than the Qc at an equal dose (p<0,05). Conclusion: This finding suggests that quercetin administered as a preventive measure (Qp) may promo
... It is also commonly known as a polyphenolic flavonoid which can be found in several edible plant that are consumed on a daily diet. As an antioxidant, it can strengthen the membrane's resistance to oxidative damage caused by free radicals (4,5). Certain commercial products containing quercetin are used as dietary supplements to promote human health. ...
Introduction: Quercetin is a flavonoid found in a variety of plants, including guava, apples, onions, and tea. It’s been used as an anti-oxidant and anti-inflammatory substance for a long time. This study aims to investigate the effect of quercetin on periodontitis caused by Porphyromonas gingivalis-adhered ligatures. Methods: Eighteen male adult Sprague Dawley rats were divided into 3 groups, namely the control group (C, n=6) and the other two groups that received quercetin at 45mg/kg/day as a preventive (Qp, n=6) and a curative treatment (Qc, n=6), respectively. Under general anaesthesia, periodontitis was induced by placing a 3/0 non-resorbable sterile silk thread around the mandibular incisor teeth of eighteen male adult Sprague Dawley rats. The ligature placement caused severe irritation in the periodontal tissue. The animals were euthanized after 14 days of post-induction treatment, and samples of the mandibular portion were kept in formalin and prepared for histological processing to determine the grade of inflammation (GI). The periodontal pocket depth (PPD) was measured using the Michigan-O probe with Williams marks at the mesial and lingual sites of the rat’s incisors tooth to determine the clinical parameter. Results: Qp showed the best improvement, in both parameters, clinically (PPD score, p=0,0018 at the lingual site, and p=0,0264 at the mesial site) and histologically (GI, p=0,0002). Significant differences were found in preventing clinical attachment-loss statistically (p<0,05) on Qp, better than the Qc at an equal dose (p<0,05). Conclusion: This finding suggests that quercetin administered as a preventive measure (Qp) may promote the healing process of gingiva in periodontitis conditions better than the control group and curative group (Qc).
... The antioxidant activities of NG-HNop and pure NG were determined as per the reported DPPH method with slight modification [30]. Stock solutions of pure NG and NG-HNop were prepared separately at concentrations of 1 mg/mL. ...
Naringin (NG), is a poorly water-soluble flavonoid that has reported to possess a variety of therapeutic efficacies. The present research work is designed to prepare and optimize Naringin hybrid nanoparticles (NG-HNs) using lipid (A), chitosan (B), and D-α-tocopheryl polyethylene glycol succinate (C). The formulations were optimized using a Box–Behnken Design (BBD), and the selection of optimized composition (NG-HNop) was carried out on the basis of low particle size (Y1) and high entrapment efficiency (Y2) using the point prediction method. The selected NG-HNop was further evaluated in order to study permeation, drug release, antimicrobial and antioxidant effect, and cell viability. The optimized nanoparticles (NG-HNop) showed a particle size and entrapment efficiency of 246 ± 8.3 nm and 83.5 ± 2.1%, with a polydispersibility index (PDI) of 0.23 and a Zeta potential of + 18.1 mV, indicating high stability. The optimized NG-HNop exhibited better drug release (89.62 ± 4.54%) and enhanced permeation (3.7 folds). A significant improvement in the antimicrobial activity was achieved against Escherichia coli with respect to Staphylococcus aureus with the hybrid nanoparticles. They also exhibited better activity in the tested cell line. On the basis of the study results, hybrid nanoparticles of Naringin are an alternative oral delivery method for treating cancer cells.
... Later, the authors investigated Eudragit as a coating agent in order to obtain pH-dependent release characteristics. Selective breakdown of the polymer facilitated QCT release at intestinal pH enough to neutralize high ROS levels (Caddeo et al., 2019). ...
Oxidative stress has been implicated in tumorigenic, cardiovascular, neuro-, and age-related degenerative changes. Antioxidants minimize the oxidative damage through neutralization of reactive oxygen species (ROS) and other causative agents. Ever since the emergence of COVID-19, plant-derived antioxidants have received enormous attention, particularly in the Indian subcontinent. Quercetin (QCT), a bio-flavonoid, exists in the glycosylated form in fruits, berries and vegetables. The antioxidant potential of QCT analogs relates to the number of free hydroxyl groups in their structure. Despite presence of these groups, QCT exhibits substantial hydrophobicity. Formulation scientists have tested nanotechnology-based approaches for its improved solubilization and delivery to the intended site of action. By the virtue of its hydrophobicity, QCT gets encapsulated in nanocarriers carrying hydrophobic domains. Apart from passive accumulation, active uptake of such formulations into the target cells can be facilitated through well-studied functionalization strategies. In this review, we have discussed the approaches of improving solubilization and bioavailability of QCT with the use of nanoformulations.
... ✓ No toxic solvents ✓ Application of low shear forces ✓ Possibility of large-scale production ⨯ Time-consuming process (continued on next page) S.R. Falsafi et al. aqueous phases and the hydrophobic zones direct toward one another, creating the internal compartment of the vesicle membrane (Caddeo et al., 2019). A unique feature of these structures for bioactive delivery is their potential in entrapping both hydrosoluble and liposoluble bioactives concurrently within the aqueous core and the lipid bilayer, respectively. ...
... On the other hand, vesicle fusion can lead to the formation of larger vesicles and sedimentation phenomenon. Ultimately, the phase separation of liposoluble bioactives from lipid bilayer may take place resulted from either lipid degradation or temperature fluctuations, causing the bioactive leakage from liposomal cargos [14,65]. Therefore, how to minimize the sensitivity to harmful agents and attain effective use of these vehicles is still attracting growing interest. ...
As unique biopolymeric architectures, covalently and electrostatically protein-polysaccharide (PRO-POL) systems can be utilized for bioactive delivery by virtue of their featured structures and unique physicochemical attributes. PRO-POL systems (i. e, microscopic /nano-dimensional multipolymer particles, molecularly conjugated vehicles, hydrogels/nanogels/oleogels/emulgels, biofunctional films, multilayer emulsion-based delivery systems, particles for Pickering emulsions, and multilayer coated liposomal nanocarriers) possess a number of outstanding attributes, like biocompatibility, biodegradability, and bioavailability with low toxicity that qualify them as powerful agents for the delivery of different bioactive ingredients. To take benefits from these systems, an in-depth understanding of the chemical conjugates and physical complexes of the PRO-POL systems is crucial. In this review, we offer a comprehensive study concerning the unique properties of covalently/electrostatically PRO-POL systems and introduce emerging platforms to fabricate relevant nanocarriers for encapsulation of bioactive components along with a subsequent sustained/controlled release.
... Accordingly, the objective of this study was to investigate the effect of Eudragit-coated microemulsion for enhanced bioavailability and efficacy of spiramycin against chronic toxoplasmosis. Eudragit was selected as the coating polymer based on previous literature reports which showed its success in coating liposomal system with subsequent protection from gastrointestinal conditions [28,29]. ...
The study investigated Eudragit coated microemulsion (ME) for oral delivery of spiramycin in treatment of toxoplasmic encephalitis. The goal was to augment the efficacy of ME by protection from gastrointestinal conditions and/or providing bioadhesion. Uncoated and coated MEs comprise labrafil as oil, cremophore EL as surfactant and labrasol as cosurfactant were prepared. The MEs were characterized with respect to shape, droplet size and in vitro drug release. Optimum formulations were assessed against cerebral toxoplasmosis. This involved oral administration of spiramycin solution, uncoated and coated MEs to Me49 Toxoplasma gondii infected mice at early and late stages. The uncoated ME droplets were spherical with average size of 147 nm. The coated ME droplets were polygonal with average size of 142 nm. Spiramycin release rate was significantly higher from uncoated ME. The parasitic load and histopathology reflected superiority of spiramycin coated ME over uncoated ME and both were more effective than spiramycin solution. The same trend was evident in early and late stages of infection. Interestingly, all formulations showed better efficiency in late stage of infection. The study introduced eudragit coating of ME as a tool to augment oral delivery from microemulsions. The developed system hastened the efficacy of spiramycin against toxoplasmic encephalitis.
... ✓ No toxic solvents ✓ Application of low shear forces ✓ Possibility of large-scale production ⨯ Time-consuming process (continued on next page) S.R. Falsafi et al. aqueous phases and the hydrophobic zones direct toward one another, creating the internal compartment of the vesicle membrane (Caddeo et al., 2019). A unique feature of these structures for bioactive delivery is their potential in entrapping both hydrosoluble and liposoluble bioactives concurrently within the aqueous core and the lipid bilayer, respectively. ...
Background
Lycopene, as a promising biofunctional ingredient in human diet, is attaining huge importance nowadays. Besides its critical importance as a natural colorant, more especially, it is considered as a health-promotional component that endows a multitude of advantageous features. Nonetheless, its inefficiency vs. process/environmental stresses, poor-aqueous solubility, plus poor-bioavailability are the most bottlenecks limiting food/pharma utilization. At the same time, the field of nano-dimensional bioactive delivery vehicles has developed quickly. In this scenario, the most prominent instances of such carriers are lipid-based nanoformulations (i.e., nano-/Pickering/double emulsions, surfactant-based nano-vectors, nano-structured lipid carriers (NLCs), solid lipid nano-particles (SLNs), etc.) and biopolymeric nano-structures (e.g., nano-hydrogels/organogels/oleogels, nanofibers, nanotubes, cyclodextrins, and protein-polysaccharide nanocomplexes/conjugates).
Scope and approach
To take benefit of these properties, a foundational understanding of why lycopene nanodelivery systems are such unbeatable nano-systems and how we could utilize their potentials is crucial. Here, we attempted to recount the unique features of emerging platforms of nano-carriers, which are corresponding to the lycopene loading and controlled delivery. Discussion was also extended to cover the innovative progress in nanoencapsulation of lycopene with an emphasis on the factors influencing its bioaccessibility in such nanovehicles, together with their shortcomings and upcoming evolutions.
Key findings and conclusions
Biopolymeric and lipid-based nano-structures, as attractive and effectual nanovehicles, have demonstrated to be potential strategies for the protection of lycopene throughout the digestive system along with representing an efficacious targeted release.
... • Aqueous solubility of quercetin was 35.1 times higher when complexed with Et-β-CD Photostability and antioxidant activity was improved Park et al. (2017) Size reduction Quercetin nanosuspension Wet media milling • Particle size reduction improved the quercetin solubility up to 10-fold, which is relatable to improved bioavailability Manca et al. (2020) Quercetin nanocrystals Antisolvent precipitation • Solubility of quercetin nanocrystals were found to be 5-fold higher than pure quercetin Hot melt extrusion • Quercetin that passes through the artificial membrane, thus bioavailability, was increased thanks to its amorphous structure encouraged by HPMC • Peak plasma concentration was also increased Shi et al. (2020) Chitosan oligosaccharide Co-milling • Dissolution behaviour of quercetin was improved under both sink and non-sink conditions • Increased quercetin concentration in amorphous structures were reported to improve bioavailability • Up to 2.25 times higher quercetin content was reported in rats blood plasma compared to pure quercetin Han et al. (2020) breakdown in the small intestine due to the presence of bile salts and the hydrolysis of the phospholipids by phospholipases (Liu, Wei, Ye, Tian, & Han, 2017). There have been numerous studies on the ability of liposomes to increase the bioavailability and bioactivity of quercetin (Liu et al., 2020e;Chen et al., 2019; Román-Aguirre, Leyva-Porras, Cruz-Alcantar, Aguilar-Elguézabal, & Saavedra-Leos, 2020; Caddeo et al., 2019). In one study, quercetin-loaded liposomes were trapped within chitosan microgels, which increased the bioavailability of the quercetin under simulated gastrointestinal tract conditions compared to simple liposomes alone (Huang, Wang, Chu, & Xia, 2020). ...
Background
Natural antioxidants, such as polyphenols, are finding increasing application in functional foods designed to improve human health, wellbeing, and performance. Quercetin is a flavonol-based polyphenol that exhibits a broad range of potentially beneficial health effects, including anti-hypertensive, anti-diabetic, anti-asthmatic, anti-carcinogenic, anti-viral and antioxidant activities. The types and amounts of quercetin found in different plant sources vary considerably. Onions have a particularly high quercetin content, mainly in the form of isoquercetin, whereas black teas and apples mainly contain quercetin in the form of rutin.
Scope and approach
Quercetin has been incorporated into different kinds of food matrices to improve their nutritional profiles, including baked goods and dairy products. However, the bioavailability of quercetin is often relatively low (<10%) because of its poor water-solubility, chemical stability, and absorption profile. The bioavailability of quercetin depends on its chemical structure, physicochemical properties, and food matrix effects.
Key findings and conclusions
A number of studies have shown that the bioavailability of quercetin can be improved by encapsulating it in well-designed colloidal delivery systems assembled from food-grade ingredients. This review summarizes the major factors affecting the bioavailability of quercetin, as well as approaches being developed to increase its bioavailability. Enhancing the bioavailability of quercetin may lead to the development of more effective nutraceuticals and functional foods.
In this study, we have co-loaded atorvastatin (ATR) and quercetin (QCT) in a nonionic microemulsion. After developing a derivative ratio spectrophotometric technique for simultaneous analysis of ATR and QCT, pseudoternary phase diagram was constructed utilizing 1:4 d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and ethanol as surfactant and cosurfactant, respectively. Oleic acid was used as oil phase. Structural characterization of the formulation was carried out along a water dilution line created in monophasic region. Characterizations at these dilution points were performed using dynamic light scattering and polarized light microscopy. The average hydrodynamic size of the optimized formulation was found to be 18.9 nm and it did not change upon loading of ATR and QCT. In vitro release was assessed for the formulations loaded with different ratios of ATR and QCT, and the data were fitted to different mathematical models. Interestingly, we noticed differences in release kinetics during changes in dose ratios, particularly for QCT. Higuchi kinetics, observed at equal dose, shifted to Korsmeyer-Peppas model at higher QCT-ATR ratio (2:1 and 4:1). This difference is attributable to the ability of QCT molecules of overwhelming the interface at higher concentrations. Altogether, our observations highlight that the ratio of payloads should be selected carefully in order to avoid unpredictable release patterns.
To maintain the freshness of the fruit during storage, sodium alginate/carboxymethyl cellulose films embedded with pH-senstive liposomes encapsulated green tea extract were developed (SA/CMC/TP-Lip). An orthogonal design was used to optimise the preparation of TP-Lip and SA/CMC/TP-Lip was prepared through response surface. The stability of TP-Lip structure was measured. The morphology of SA/CMC/TP-Lip was characterised by SEM, and the mechanical properties and oxidation resistance of films were measured. Special attention was paid to the pH sensitivity of TP-Lip and the improvement of film properties. The zeta potential and encapsulation rate of TP-Lip were −45.85 ± 2.13 mV and 61.45 ± 0.23%. The average release rate of TP encapsulated into TP-Lip at pH 3 was 41.08%, an increase of 23.07% over pH 6 during 12 h. SEM and FTIR showed that TP-Lip was structurally stable and had good compatibility with SA/CMC. Tensile strength was increased by 30.55% and DPPH radical scavenging capacity was increased by 7.16% with the addition of TP-Lip. SA/CMC/TP-Lip is applied to blueberries to reduce their weight loss and improve the loss of freshness of blueberries during storage. Thus, SA/CMC/TP-Lip could provide a new way to extend active packaging materials and maintain fruit freshness during storage.
In this study, a magnetic core–shell metal–organic framework (MOF) nanocomposite, Fe3O4-COOH@UiO-66-NH2, was synthesized for tumor-targeting drug delivery by incorporating carboxylate groups as functional groups onto ferrite nanoparticle surfaces, followed by fabrication of the UiO-66-NH2 shell using a facile self-assembly approach. The anticancer drug quercetin (QU) was loaded into the magnetic core–shell nanoparticles. The synthesized magnetic nanoparticles were comprehensively evaluated through multiple techniques, including FT-IR, PXRD, FE-SEM, TEM, EDX, BET, UV–vis, ZP, and VSM. Drug release investigations were conducted to investigate the release behavior of QU from the nanocomposite at two different pH values (7.4 and 5.4). The results revealed that QU@Fe3O4-COOH@UiO-66-NH2 exhibited a high loading capacity of 43.1% and pH-dependent release behavior, maintaining sustained release characteristics over a prolonged duration of 11 days. Furthermore, cytotoxicity assays using the human breast cancer cell line MDA-MB-231 and the normal cell line HEK-293 were performed to evaluate the cytotoxic effects of QU, UiO-66-NH2, Fe3O4-COOH, Fe3O4-COOH@UiO-66-NH2, and QU@Fe3O4-COOH@UiO-66-NH2. Treatment with QU@Fe3O4-COOH@UiO-66-NH2 substantially reduced the cell viability in cancerous MDA-MB-231 cells. Cellular uptake and cell death mechanisms were further investigated, demonstrating the internalization of QU@Fe3O4-COOH@UiO-66-NH2 by cancer cells and the induction of cancer cell death through the apoptosis pathway. These findings highlight the considerable potential of Fe3O4-COOH@UiO-66-NH2 as a targeted nanocarrier for the delivery of anticancer drugs.
Intestinal diseases like inflammatory bowel disease (IBD) and colorectal cancer originate from inflammation and disruption of mucosal barriers. Polyphenols can mitigate intestinal inflammation through antioxidant, anti‐inflammatory, and microbiome modulation effects. However, the poor solubility and stability of polyphenols restrict therapeutic delivery. Self‐assembly provides a nanoscale platform to overcome these limitations. Polyphenol‐based nanoparticles (PNPs) are formed via coordination of polyphenols with metals like iron, copper, and zinc based on the catechol/galloyl groups. Templeted assembly with amphiphilic block copolymers can also direct polyphenol self‐assembly into nanostructures. PNPs prepared by these mild, aqueous methods exhibit enhanced stability, pH‐responsive disassembly, high cargo‐loading capacity, and targeted accumulation in inflamed intestinal tissues. PNPs can load with hydrophobic polyphenols, drugs, genes, proteins, or probiotics and demonstrate therapeutic potential in preclinical IBD, colorectal cancer, and microbiome disorder models. Ongoing challenges include augmenting prebiotic effects, multidrug encapsulation, and engineering PNPs as biotherapeutics. Future directions involve tailored polyphenol–polymer covalent assemblies and investigating PNPs interactions with enterocytes, immune cells, and microbiota. Overall, PNPs prepared by facile self‐assembly combine the bioactivities of polyphenols with advanced delivery functionality, presenting new opportunities for combination and microbiota‐based therapies for complex intestinal diseases.
This work provides the first description of the synthesis and characterization of water-soluble chitosan (Cs) derivatives based on the conjugation of both diethylaminoethyl (DEAE) and catechol groups onto the Cs backbone (Cs-DC) in order to obtain a Cs derivative with antioxidant and antimicrobial properties. The degree of substitution [DS (%)] was 35.46% for DEAE and 2.53% for catechol, determined by spectroscopy. Changes in the molecular packing due to the incorporation of both pendant groups were described by X-ray diffraction and thermogravimetric analysis. For Cs, the crystallinity index was 59.46% and the maximum decomposition rate appeared at 309.3 °C, while for Cs-DC, the values corresponded to 16.98% and 236.4 °C, respectively. The incorporation of DEAE and catechol groups also increases the solubility of the polymer at pH > 7 without harming the antimicrobial activity displayed by the unmodified polymer. The catecholic derivatives increase the radical scavenging activity in terms of the half-maximum effective concentration (EC50). An EC50 of 1.20 μg/mL was found for neat hydrocaffeic acid (HCA) solution, while for chitosan-catechol (Cs-Ca) and Cs-DC solutions, concentrations equivalent to free HCA of 0.33 and 0.41 μg/mL were required, respectively. Cell culture results show that all Cs derivatives have low cytotoxicity, and Cs-DC showed the ability to reduce the activity of reactive oxygen species by 40% at concentrations as low as 4 μg/mL. Polymeric nanoparticles of Cs derivatives with a hydrodynamic diameter (Dh) of around 200 nm, unimodal size distributions, and a negative ζ-potential were obtained by ionotropic gelation and coated with hyaluronic acid in aqueous suspension, providing the multifunctional nanoparticles with higher stability and a narrower size distribution.
Cisplatin (CDDP) is an effective chemotherapeutic drug that has been used successfully in treating various tumors. Although its higher antineoplastic agent activity, CDDP exhibited severe side effects that limit its use. CDDP-induced toxicity is attributed to oxidative stress and inflammation. Apocynin (APO) is a bioactive phytochemical with potent antioxidant and anti-inflammatory properties. However, pharmaceutical experts face significant hurdles due to the limited bioavailability and quick elimination of APO. Therefore, we synthesized a chitosan (CTS)-based nano delivery system using the ionic gelation method to enhance APO bioactivity. CTS-APO-NPs were characterized using different physical and chemical approaches, including FTIR, XRD, TGA, Zeta-sizer, SEM, and TEM. In addition, the protective effect of CTS-APO-NPs against CDDP-induced nephrotoxicity, hepatotoxicity, and cardiotoxicity in rats was evaluated. CTS-APO-NPs restored serum biomarkers and antioxidants to their normal levels. Also, histopathological examination was used to assess the recovery of heart, kidney, and liver tissues. CTS-APO-NPs attenuated the oxidative stress mediated by Nrf2 activation while it dampened inflammation mediated by NF-κB suppression. CTS-APO-NPs is a potentially attractive target for more therapeutic trials.
Multidrug resistance (MDR) greatly hinders the efficacy of chemotherapy in a variety of hematological malignancies and solid tumors. Traditionally, Quercetin (Que) based co-delivery drugs strategies show lower water solubility and lack of motion ability for drugs active transfer. In order to overcome this disadvantage, we have developed a Janus nanomotors [email protected](DQ) for targeted combination therapy. The combined strategy could increase the intracellular accumulation of the two drugs (quercetin and doxorubicin) through the high-speed motion of the motor and higher killing rate of Dox on MCF-7/Adr cells by using quercetin. By reversing Dox resistance, [email protected](DQ), could achieve lower RI values (8.1) and higher RF values (6.8) in MCF-7/Adr cells compared to free Dox, which means [email protected] (DQ) is effective against multidrug resistance. This work exhibits a novel nanoplatform, which could not only load chemotherapy drugs efficiently, but could also improve the effect of chemotherapy drugs by overcoming MDR.
As a result of their unique physical properties, biological membrane mimetics such as biopolymers are used in a broad range of scientific and technological applications. This comprehensive book covers new applications of biopolymers in the research and development of industrial scale nutraceutical and functional food grade products. All the major food biopolymers are included, from plant, animal and marine sources. Coverage also includes biopolymer-based drug delivery mechanisms intended for biological applications such as bio-detection of pathogens, fluorescent biological labels, and drug and gene delivery.
This is the first interdisciplinary book to address this area specifically and is essential reading for those who produce the functional biopolymer materials as well as those who seek to incorporate them into appropriate nutraceutical, food and drug delivery products.
Phytonutrients (plant chemicals) called flavonoids may be detected in almost all fruits and vegetables. They are responsible for the brilliant colors of fruits and vegetables, together with carotenoids. Flavonoids, like other phytonutrients, are potent antioxidants with antiinflammatory and immune-enhancing characteristics. Polyphenols may diminish severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by linking to the angiotensin-converting enzyme 2 (ACE-2) linking site and limiting viral entrance, as well as regulating the severity of COVID-19 lung destruction by controlling ACE-2 expression. A new potential relationship between SARS-CoV-2 and the co-receptor dipeptidyl peptidase 4 (DPP4) may induce the expansion of newer COVID-19 treatment methods, in addition to ACE-2. After glycosylation, flavonoids' solubility in water is significantly enhanced, which increases their pharmacological actions. Antioxidant and antiinflammatory effects have been discovered in resveratrol (RSV). Quercetin was discovered to have a possible repressing consequence against SARS-CoV-2 in a computer simulation. Main protease (Mpro) had a significant preference for quercetin. According to a computer study, the flavonoids icariin, myricitrin, naringin, quercitrin, and neohesperidin have a significant interaction potential for transmembrane protease serine 2 (TMPRSS2). The bioavailability improvement of quercetin has also been shown in vivo. The novel nanovesicles exhibited extended drug durability and significant therapeutic impact compared to uncoated ones due to chitosan resistance to stomach acid. This chapter aims to explain the use of flavonoids and other polyphenols against SARS-CoV-2.
Supplying sufficient oxygen within the scaffolds is one of the essential hindrances in tissue engineering that can be resolved by oxygen‐generating biomaterials (OGBs). Two main issues related to OGBs are controlling oxygenation and reactive oxygen species (ROS). To address these concerns, we developed a composite scaffold entailing three layers (hydrogel‐electrospun fibers‐hydrogel) with antioxidant and antibacterial properties. The fibers, the middle layer, reinforced the composite structure, enhancing the mechanical strength from 4.27 ± 0.15 to 8.27 ± 0.25 kPa; also, this layer is made of calcium peroxide and silk fibroin (SF) through electrospinning, which enables oxygen delivery. The first and third layers are physical SF hydrogels to control oxygen release, containing quercetin (Q), a nonenzymatic antioxidant. This composite scaffold resulted in almost more than 40 mmHg of oxygen release for at least 13 days, and compared with similar studies is in a high range. Here, Q was used for the first time for an OGB to scavenge the possible ROS. Q delivery not only led to antioxidant activity but also stabilized oxygen release and enhanced cell viability. Based on the given results, this composite scaffold can be introduced as a safe and controllable oxygen supplier, which is promising for tissue engineering applications, particularly for bone.
Encapsulation of natural bio-actives or fermented foods has been a booming area in the field of the food industry. They are commonly utilized in food formulation regarding the health benefits. Nano and capsulated techniques are designed to engineer the effective immune and digestive systems of a human being. This chapter discusses different nanoencapsulation approaches for enhancing the function of supplemented foods. Encapsulating foods composes an area where the selection of appropriate bioactive and pigmentation are done with the help of the nano technique. Pigmentation in the food sector is difficult, as it must work well with a variety of flavors and nutrients of the food. It also highlights how using colors in the food sector is a superior alternative. It overviews the microbial food colorants.
Skeletal muscle tissue cannot repair itself after volumetric muscle loss (VML) injury, which results in chronic inflammation and secondary injuries. Quercetin (QCN) possesses natural antioxidant properties and the ability of suppressing inflammation. Herein, an in situ photocurable composite hydrogel was developed by employing silk fibroin methacryloyl (SilMA) and decellularized extracellular matrix (ECM) derived from skeletal muscle. QCN loaded liposomes were introduced to create a local microenvironment which was conducive to skeletal muscle regeneration by regulating M2 polarization of macrophages and reducing oxidative stress. The SilMA-ECM-QCN composite hydrogel was characterized with suitable porosity, mechanical properties and degradation properties, as well as adhesion property for injury wound sealing via in situ polymerization. Moreover, the therapeutic effects of SilMA-ECM-QCN for promoting muscle regeneration and decreasing fibrosis were demonstrated by using a VML rat model. The results showed that the photocurable SilMA-ECM-QCN hydrogel had a huge advantage in the rapid filling of complex skeletal muscle tissue defects. Altogether, the present work could provide a promising strategy to create a pro-regenerative microenvironment for muscle regeneration by utilizing natural biomaterials.
Liposomal formulations, as versatile nanocarrier systems suitable for targeted delivery, have a highly focused role in the therapy development of unmet clinical needs and diagnostic imaging techniques. Formulating nanomedicine with suitable zeta potential is an essential but challenging task. Formulations with a minimum ±30 mV zeta potential are considered stable. The charge of the phospholipid bilayer can be adjusted with membrane additives. The present Quality by Design-derived study aimed to optimise liposomal formulations prepared via the thin-film hydration technique by applying stearylamine (SA) or dicetyl phosphate (DCP) as charge imparting agents. This 32 fractional factorial design-based study determined phosphatidylcholine, cholesterol, and SA/DCP molar ratios for liposomes with characteristics meeting the formulation requirements. The polynomials describing the effects on the zeta potential were calculated. The optimal molar ratios of the lipids were given as 12.0:5.0:5.0 for the SA-PBS pH 5.6 (optimised sample containing stearylamine) and 8.5:4.5:6.5 for the DCP-PBS pH 5.6 (optimised sample containing dicetyl phosphate) particles hydrated with phosphate-buffered saline pH 5.6. The SA-PBS pH 5.6 liposomes had a vesicle size of 108 ± 15 nm, 0.20 ± 0.04 polydispersity index, and +30.1 ± 1.2 mV zeta potential, while these values were given as 88 ± 14 nm, 0.21 ± 0.02, and −36.7 ± 3.3 mV for the DCP-PBS pH 5.6 vesicles. The prepared liposomes acquired the requirements of the zeta potential for stable formulations.
Polyphenols are secondary metabolites, naturally found in plants. They are typically known for their antioxidant activity and beneficial impact on health. Extraction of polyphenols from biological matrices is the first step toward their valorization. Many methods of separation (chromatography) are used to separate the polyphenols from the undesirable fraction of the extract. Moreover, the increasing interest in the isolation (e.g., ultrafiltration, nanofiltration) techniques for the purification of polyphenols is mainly due to their potential applications as natural antioxidants in food, pharmaceutical, and cosmetic industries. Many preservation methods (e.g., drying, encapsulation) are required to maintain their biological activities throughout the process. Finally, and after the recovery of polyphenols and their purification, colorimetric, chromatographic and spectrometric methods (LC-MS, GC-MS-MS) are used to identify and characterize polyphenols. This chapter discusses the methodologies used for separation, purification, analysis, and preservation of polyphenols.
Phenolics are among the most studied compounds due to their beneficial implications in human health. The conventional methods applied in the extraction of these compounds include maceration, distillation, Soxhlet, among others, and the extraction capacity depends on several factors, such as the extraction solvent and respective concentration, time, and temperature. The incorporation of green chemistry in the development of more sustainable products and processes has promoted the use of new solvents that would replace conventional ones and the application of more eco-sustainable technologies (e.g., supercritical fluids, pulsed electric fields, and ultrasounds). Green solvents, coupled with conventional extraction methods, present excellent stability for food, pharmaceutical, and cosmetic industries because they are non-toxic, non-volatile, recyclable, biodegradable, and imply lower energy cost of synthesis. In this chapter, traditional and eco-sustainable methods based on solid–liquid extraction will be revised, as well as safety issues, life-cycle assessment, and economic aspects.
Liposomes nowadays have become preferential drug delivery system, since it provides facilitating properties to drugs such as improved therapeutic index of encapsulated drug, target and controlled drug delivery, and less toxicity. However, conventional liposomes have shown some disadvantages such as less drug loading capacity, poor retention, clearance by kidney or reticuloendothelial system, and less release of hydrophilic drugs. Thus, to overcome these disadvantages recently, scientists have explored new approaches and methods viz. ligand conjugation, polymer coating, and liposomes-hybrid including surface-modified liposomes, biopolymer-incorporated liposomes, guest-in-cyclodextrin-in-liposome, liposome-in-hydrogel, liposome-in-film, and liposome-in-nanofiber, etc. These approaches have been shown to improve the physiochemical and pharmacokinetic properties of encapsulated drugs. Lately, Pharmacokinetic-pharmacodynamic (PK–PD) computational modeling has emerged as a beneficial tool for analyzing the impact of formulation- and system-specific factors on the target disposition and therapeutic efficacy of liposomal drugs. There has been an increasing number of liposome-based therapeutic drugs, both FDA approved and undergoing clinical trials having application in anticancer, Alzheimer's, diabetes, and glaucoma. To meet the continuous demand of health sectors and to produce the desired product, it is important to perform pharmacokinetic studies. This review focuses on the physical, physicochemical, and chemical factors of drugs that influence the target delivery of drugs. It also explains various physiological barriers such as systemic clearance, and extravasation. A novel approach, liposomal-hybrid complex: an innovative approach as a vesicular drug delivery system to overcome limited membrane permeability and bioavailability has been discussed in the review. Moreover, this review highlights the pharmacokinetic considerations and challenges of poorly absorbed drugs along with the applications of a liposomal delivery system in improving PKPD in various diseases such as cancer, Alzheimer's, diabetes, and glaucoma.
The incompetence of the current management of ulcerative colitis (UC) demands novel pharmaceutical techniques and advance therapeutic strategies to facilitate safe and efficacious treatment of the disease. In this quest, mesalazine, a 5-aminosalicylate with anti-inflammatory and potent antioxidant activities, along with curcumin, a natural anti-inflammatory and antioxidant polyphenol, were found to produce a synergistic efficacy to efficiently alleviate UC. In the current research, we have formulated pH-sensitive liposomes containing a low-dose combination of mesalazine and curcumin as a potential therapy for UC. It was hypothesized that the synergistic action of the two drugs, pH-dependent colon-specific delivery, and use of liposomes as a nano-technological drug carrier system would diminish drug-associated side effects, reduce the total administration dose, and provide efficacious and instant relief from UC. The hypothesis was validated using guinea pig model of mild-moderate UC, where pH-sensitive MZ-CM co-loaded liposomes were found to be more efficacious than single-drug liposomes or drug's solution form. Furthermore, both drugs exhibited high antioxidant activity and mitigated the oxidative stress present along UC; hence, prompted an instantaneous treatment of UC. We, therefore, validate that eudragit-S100 coated MZ-CM liposomes is a promising therapy that needs to be developed as a marketed product for the treatment of UC.
Bioactive compounds (bioactives) derived from plants and animals, are effective in increasing the safety and health of society through the treatment and prevention of diseases such as cancer. Fortifying conventional foods with bioactives is an accepted strategy by scientists, food manufacturers, and consumers. Milk and dairy products are among the most important foods used in our daily diet and can be a suitable option to deliver bioactives to the body, but there are challenges towards using these compounds in their original unprotected/free form. They can be degraded before reaching the target location in the body and interact with milk compounds, resulting in a negative impact on the quality characteristics of the corresponding foods. Thus, a suitable encapsulation technique can help to protect these sensitive compounds from environmental stresses and the process they encounter during the manufacture of food. This also prevents adverse interactions of bioactives with compounds in milk. This article aimed to review the recent literature about the addition of encapsulated bioactives such as vitamins, essential fatty acids, phenolic compounds, minerals, and enzymes into milk and dairy products, with a focus on common applied bioactives, methods of encapsulation, the interaction of bioactives with milk components, and the challenges facing the use of this technology in the dairy industry.
Pelargonidin-3-O-glucoside (Pg) is a well-known anthocyanin derivative possessing potential biological activity. Nonetheless, the bioactivity of Pg is limited due to instability in the physiological environment. Functionalized nanoliposomes using chitosan and/or pectin coating is an excellent carrier system for nanoencapsulation of food bioactive compounds such as Pg. Therefore, this study aimed to investigate the protective effect of Pg-loaded pectin–chitosan coated nanoliposomes against palmitic acid (PA)-induced hepatocytes injury in L02 cells. Firstly, Pg-loaded pectin–chitosan coated nanoliposomes were characterized using the DLS, HPLC, TEM, and cellular uptake study in L02 cells. Thereafter, we assayed the protective effect against PA-induced lipotoxicity, ROS and O2- generation, mitochondrial dysfunction (MMP), and GSH depletion. Results showed that Pg-loaded nanoliposomes significantly reduced the PA-induced L02 cells toxicity via suppressing ROS production, O2- generation, MMP collapse, and GSH reduction, whereas the free-Pg samples were not effective. On the contrary, the chitosan and/or pectin coated nanoliposomes showed higher results compared to coating-free nanoliposomes. Altogether, the results of our study ensured that
Pg-loaded pectin–chitosan coated nanoliposomes was capable of reducing PA-induced hepatocytes injury. Thus, pectin–chitosan coated nanoliposomes can be useful for hepatocellular delivery of hydrophilic compounds with greater biological activity.
Quercetin, which is present in numerous fruits and vegetables, has shown promise in improving inflammation, lipid profiles, and blood pressure in humans. However, the efficacy of quercetin in diabetic nephropathy (DN) remains preclinical and unclear. Therefore, a meta-analysis based on preclinical animal data is needed to assess the efficacy, optimal dosage, and underlying mechanism of DN treatment to accelerate new drug research and clinical translation. We conducted a literature search in PubMed, Embase, Web of Science, and Cochrane Library to retrieve randomized controlled trials evaluating the effects of quercetin in rat or mouse diabetic models. We assessed the quality of the studies individually according to SYRCLE's risk of bias tool for animal studies. Twenty animal studies, including 378 animals, were included in the meta-analysis. Meta-analysis data showed that renal function indices, such as renal index, urine protein, uric acid, urine albumin, and serum creatinine levels, significantly improved with quercetin administration. However, no significant association was observed between quercetin and creatinine clearance. Quercetin remarkably alleviated oxidative stress by reducing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) and catalase (CAT) activities. In addition, quercetin exhibits anti-inflammatory activity by reducing tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）levels. Subgroup analysis performed using quercetin doses and animal species indicated that animal species were a source of heterogeneity. This meta-analysis suggests that quercetin is a promising drug for DN treatment, facilitating clinical prediction and therapy.
Liposomes are one of the most studied and most promising nanocarriers to date, representing a biocompatible, safe, and efficient delivery system for both hydrophilic and lipophilic compounds.
This work aimed to evaluate the efficacy in encapsulating an aqueous extract of Lisosan G (LG), a Triticum aestivum whole grains fermented powder with strong antioxidant activity, into Eudragit-liposomes designed for oral delivery.
The total phenolics and the antioxidant activity of LG extract and LG extract encapsulated in Eudragit-liposomes were evaluated by the Folin-Ciocalteu, DPPH, and FRAP colorimetric assays. Finally, the biological activity of both LG formulations was assessed as human erythrocytes protection from oxidative stress through the cellular antioxidant activity (CAA) assay.
Our results demonstrate that the encapsulation into Eudragit-liposomes preserved the phenolics content of LG extract and retained its antioxidant properties both in vitro and ex vivo. Furthermore, LG Eudragit-liposomes exhibited increased ferric reducing capacity and protection of human erythrocytes from oxidative insult, probably due to the antioxidant properties of liposome constituents.
Therefore, the encapsulation into Eudragit-liposomes represents an excellent strategy to prevent possible reduction and loss of activity of LG bioactive compounds, and to deliver them via oral administration.
Toxicity caused by the exposure to human-made chemicals and environmental conditions has become a major health concern because they may significantly increase the formation of reactive oxygen species (ROS), negatively affecting the endogenous antioxidant defense. Living systems have evolved complex antioxidant mechanisms to protect cells from oxidative conditions. Although oxidative stress contributes to various pathologies, the intake of molecules such as polyphenols, obtained from natural sources, may limit their effects because of their antioxidant and antimicrobial properties against lipid peroxidation and against a broad range of foodborne pathogens. Ingestion of polyphenol-rich foods, such as fruits and vegetables, help to reduce the harmful effects of ROS, but the use of supramolecular and nanomaterials as delivery systems has emerged as an efficient method to improve their pharmacological and therapeutic effects. Suitable exogenous polyphenolic antioxidants should be readily absorbed and delivered to sites where pathological oxidative damage may take place, for instance, intracellular locations. Many potential antioxidants have a poor bioavailability, but they can be encapsulated to improve their ideal solubility and permeability profile. Development of effective antioxidant strategies requires the creation of new nanoscale drug delivery systems to significantly reduce oxidative stress. In this review we provide an overview of the oxidative stress process, highlight some properties of ROS, and discuss the role of natural polyphenols as bioactives in controlling the overproduction of ROS and bacterial and fungal growth, paying special attention to their encapsulation in suitable delivery systems and to their location in colloidal systems where interfaces play a crucial role.
The present study aimed to develop and optimize liposome formulation for the colonic delivery of biologically active compounds. A strategy to facilitate such targeting is to formulate liposomes with a polymer coating sensitive to the pH shifts in the gastrointestinal tract. To this end, liposomes encapsulating curcumin-chosen as the biologically active compound model-and coated with the pH-responsive polymer Eudragit S100 were prepared and characterized. Curcumin was encapsulated into small unilamellar vesicles (SUVs) by the micelle-to-vesicle transition method (MVT) in a simple and organic solvent-free way. Curcumin-loaded liposomes were coated with Eudragit S100 by a fast and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and curcumin antioxidant activity. In particular, curcumin-loaded liposomes displayed size lower than 100 nm, encapsulation efficiency of 98%, high stability at both 4 °C and 25 °C, high in vitro antioxidant activity, and a cumulative release that was completed within 200 min. A good Eudragit S100 coating which did not alter the properties of the curcumin-loaded liposomes was obtained. The present work therefore provides a fast and solvent-free method to prepare pH-responsive polymer-coated liposomes for the colonic delivery of biologically active compounds.
This study focused on an extract from fermented flour from the Lady Joy variety of the common bean Phaseolus vulgaris. The extract, Lady Joy lysate (Lys LJ), is enriched in antioxidant compounds during the fermentation. We assessed it for its protective effect on endothelial cells treated with oxidized-LDL (ox-LDL). The oxidative stress was determined by measuring the contents of thiobarbituric acid-reactive substances and reactive oxygen metabolites. ICAM-1, ET-1 and IL-6 concentrations were assessed using ELISA. LOX-1 and CHOP expression were analyzed using both quantitative RT-PCR and ELISA or western blotting. Ox-LDL treatment induced significant oxidative stress, which was strongly reduced by pre-treatment with the extract. The ox-LDL exposure significantly enhanced ICAM-1, IL-6 and ET-1 levels over basal levels. Lys LJ pre-treatment exerted an inhibitory effect on ox-LDL-induced endothelial activation with ICAM-1 levels comparable to those for the untreated cells. IL-6 and ET-1 production, although reduced, was still significantly higher than for the control. Both LOX-1 and CHOP expression were upregulated after ox-LDL exposure, but this effect was significantly decreased after Lys LJ pre-treatment. Lys LJ alone did not alter the ICAM-1, IL-6 and ET-1 concentrations or CHOP expression, but it did significantly lower the LOX-1 protein level. Our data suggest that Lys LJ is an effective antioxidant that is able to inhibit the oxidation process, but that it is only marginally active against inflammation and ET-1 production in HMEC-1 exposed to ox-LDL.
In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.
Cardiovascular disease is a major cause of death worldwide despite the majority of its risk factors being preventable and treatable. The results of numerous epidemiological studies suggest that a diet rich in fruits and vegetables affords protection against CVD, and this may be attributed, in part, to the flavonoid quercetin. The aims of this review are to summarise the current knowledge on the bioavailability and metabolism of quercetin as well as discuss the current evidence behind the potential mechanisms by which quercetin exerts its cardioprotective effects. This review summarises key human studies administering quercetin that have been published to date. Although interesting results have been seen in animal and cell culture studies, in general, these have not been replicated in human trials. Several studies have, however, shown that quercetin can reduce blood pressure in hypertensive patients. The exact mechanisms are yet to be elucidated. Further studies are required to investigate the use of quercetin as a cardioprotective treatment, in particular long-term and dose–response studies.
As the role of monocytes and macrophages in a range of diseases is better understood, strategies to target these cell types are of growing importance both scientifically and therapeutically. As particulate carriers, liposomes naturally target cells of the mononuclear phagocytic system (MPS), particularly macrophages. Loading drugs into liposomes can therefore offer an efficient means of drug targeting to MPS cells. Physicochemical properties including size, charge and lipid composition can have a very significant effect on the efficiency with which liposomes target MPS cells. MPS cells express a range of receptors including scavenger receptors, integrins, mannose receptors and Fc-receptors that can be targeted by the addition of ligands to liposome surfaces. These ligands include peptides, antibodies and lectins and have the advantages of increasing target specificity and avoiding the need for cationic lipids to trigger intracellular delivery. The goal for targeting monocytes/macrophages using liposomes includes not only drug delivery but also potentially a role in cell ablation and cell activation for the treatment of conditions including cancer, atherosclerosis, HIV, and chronic inflammation.
Development of liposomal mucoadhesive drug delivery system, which is able to improve the bioavailability of poorly absorbed oral drugs by prolonging their gastric and intestinal residence time, through facilitating the intimate contact of the delivery system with the absorption membrane.
Liposomes containing model drug atenolol were prepared by the modified ethanol injection method. Liposomes containing atenolol were coated by different mucoadhesive polymers, for example, chitosan, Carbopol 974P, Eudragit L100, and Eudragit S100, to optimize the choice of coating material. The delivery systems were tested for their in vitro mucoadhesiveness.
Liposomes prepared by the ethanol injection method were of satisfactory size (around 100 nm, before coating). Through the coating of liposomes in the presence of unentrapped material, the entrapment efficiency for drug was increased. In vitro mucoadhesive test confirmed the mucoadhesive properties of the coated layer for all tested polymers; however, Eudragit S100-coated liposomes were superior to other coating materials.
Eudragit coating appeared to be an optimal polymer choice. These preliminary data indicate that polymer-coated mucoadhesive liposomes are able to carry sufficient amount of drug and to remain attached to the intestinal mucosa for a sufficient period of time to enable prolonged absorption of entrapped drug.
While keeping in mind that the in vivo conditions may vary with the in vitro ones, we may recommend the system described in our work for possible oral delivery of peptides and phytochemicals.
Liposomes have been used as delivery vehicles for stabilizing drugs, overcoming barriers to cellular and tissue uptake, and for directing their contents toward specific sites in vivo. Chitosan is a biological macromolecule derived from crustacean shells and has several emerging applications in drug development, obesity control, and tissue engineering. In the present work, the interaction between chitosan and dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied by transmission electron microscopy (TEM), zeta potential, solubilization using the nonionic detergent octylglucoside (OG), as well as Fourier transform infrared (FTIR) spectroscopy and viscosity measurements. The coating of DPPC liposomes by a chitosan layer was confirmed by electron microscope images and the zeta potential of liposomes. Coating of liposome by chitosan resulted in an increase in liposomal size by addition of a layer of 92 +/- 27.1 nm. The liposomal zeta potential became increasingly positive as chitosan concentration increased from 0.1 to 0.3% w/v, then it held at a relatively constant value. The amount of detergent needed to completely solubilize the liposomal membrane was increased after coating of liposomes with chitosan, indicating an increased membrane resistance to the detergent and hence a change in the natural membrane permeation properties. In the analysis of FTIR spectra of DPPC, the symmetric and antisymmetric CH(2) (at 2,800-3,000 cm(-1)) bands and the C=O (at 1,740 cm(-1)) stretching band were investigated in the absence and presence of the chitosan. It was concluded that appropriate combining of the liposomal and chitosan characteristics might be utilized for the improvement of the therapeutic efficacy of liposomes as a drug delivery system.
The purpose of this research was to investigate whether Eudragit S100 microspheres have the potential to serve as an oral carrier for peptide drugs like insulin. Microspheres were prepared using water-in oil-in water emulsion solvent evaporation technique with polysorbate 20 as a dispersing agent in the internal aqueous phase and polyvinyl alcohol (PVA)/polyvinyl pyrrolidone as a stabilizer in the external aqueous phase. The use of smaller internal aqueous-phase volume (50 microL) and external aqueous-phase volume (25 mL) containing PVA in the manufacturing process resulted in maximum encapsulation efficiency (81.8% +/- 0.9%). PVA-stabilized microspheres having maximum drug encapsulation released 2.5% insulin at pH 1.0 in 2 hours. In phosphate buffer (pH 7.4), microspheres showed an initial burst release of 22% in 1 hour with an additional 28% release in the next 5 hours. The smaller the volumes of internal and external aqueous phase, the lower the initial burst release. The release of drug from microspheres followed Higuchi kinetics. Scanning electron microscopy of PVA-stabilized microspheres demonstrated spherical particles with smooth surface, and laser diffractometry revealed a mean particle size of 32.51 +/- 20 microm. Oral administration of PVA stabilized microspheres in normal albino rabbits (equivalent to 6.6 IU insulin/kg of animal weight) demonstrated a 24% reduction in blood glucose level, with maximum plasma glucose reduction of 76 +/- 3.0% in 2 hours and effect continuing up to 6 hours. The area under the percentage glucose reduction-time curve was 93.75%. Thus, our results indicate that Eudragit S100 microspheres on oral administration can protect insulin from proteolytic degradation in the gastrointestinal tract and produce hypoglycemic effect.
The biocompatibility of cationic liposomes has led to their clinical translation in gene delivery and their application apart from cancer to cardiovascular diseases, osteoporosis, metabolic diseases, and more. We have prepared PEGylated stearyl amine (pegSA) lipoplexes meticulously considering the physicochemical properties and formulation parameters to prepare single unilamellar vesicles (SUV) of < 100 nm size which retain their SUV nature upon complexation with pDNA rather than the conventional lipoplexes which show multilamellar nature. The developed PEGylated SA lipoplexes (pegSA lipoplexes) showed a lower N/P ratio (1.5) for BMP-9 gene complexation while maintaining the SUV character with a unique shape (square and triangular lipoplexes). Colloidal and pDNA complexation stability in the presence of electrolytes and serum indicates the suitability for intravenous administration for delivery of lipoplexes to bone marrow mesenchymal stem cells through sinusoidal vessels in bone marrow. Moreover, lower charge density of lipoplexes and low oxidative stress led to lower toxicity of lipoplexes to the C2C12 cells, NIH 3T3 cells, and erythrocytes. Transfection studies showed efficient gene delivery to C2C12 cells inducing osteogenic differentiation through BMP-9 expression as shown by enhanced calcium deposition in vitro, proving the potential of lipoplexes for bone regeneration. In vivo acute toxicity studies further demonstrated safety of the developed lipoplexes. Developed pegSA lipoplexes show potential for further in vivo preclinical evaluation to establish the proof of concept.
A docetaxel (DTX) liposomal formulation composed of egg phosphatidylcholine, sodium deoxycholate, and stearylamine was developed. Eudragit (0.5%) was coated to deliver the drug to the region between the distal small intestine and the colon. Lyophilized trehalose and mannitol were used as cryoprotectants because they preserve the particle integrity and good appearance. In vitro release studies showed that the amount of drug released from the coated liposomes was low in solution 1, which simulated the pH condition of the stomach. Especially during the average gastric emptying time, the amount of drug released decreased when Eudragit was added. The plasma DTX concentration was evaluated in pharmacokinetic studies. The plasma drug concentration after intravenous (i.v.) administration decreased rapidly within 120 min. Free DTX formulated using Tween 80 and the lyophilized Eudragit-coated liposomal formulation were compared after oral administration. The oral liposomal formulation had a longer half-life (t1/2) and three-fold higher oral bioavailability. Thus, lyophilized Eudragit-coated liposomal DTX could be a promising therapy for various solid tumors to improve patient convenience and quality of life.
The present study compared the phenolic profile, the in vitro and ex vivo antioxidant activity, as well as the anti-inflammatory effect of fermented (LG) and unfermented (FG) whole wheat flour from Triticum aestivum on tumor necrosis factor alpha (TNFα)-inflamed human intestinal epithelial cells (HT-29). Gallic acid, 3-hydroxybenzoic
acid, and vanillic acid were identified by HPLC-DAD as the main polyphenols increased by fermentation. LG showed a higher antioxidant activity than FG in vitro and ex vivo. In inflamed HT-29 cells, LG exhibited a better protective effect on TNFα-induced alterations by significantly reducing the expression of IL-8 and COX-2 inflammatory mediators. Further, under inflammatory insult, LG has better normalized ROS overproduction and
strengthened the antioxidant defense system. Finally, LG and FG significantly attenuated the TNFα-induced NF-κB nuclear translocation. Our results pointed out a potential therapeutical role of LG in hardly managed intestinal inflammatory disease.
This study was designed to investigate the tumor-inhibitory effects of quercetin (Que) and its water-soluble metabolites, quercetin-3′-sulfate (Q3'S) and quercetin-3-glucuronide (Q3G), as well as to make clear the molecular mechanism and structure-antitumor relationship. It was found that Que, Q3'S and Q3G could inhibit the growth of human breast cancer MCF-7 cells in a dose-dependent manner, with IC50 values of 23.1, 27.6, and 73.2 µM, respectively, and the anticancer effect was ranked as Que > Q3'S > Q3G. Furthermore, flow cytometric assay revealed that Que, Q3'S and Q3G mediated the cell-cycle arrest principally in the S phase, and decreased the number of G0/G1 and G2/M after a 48 h of treatment with human breast MCF-7 cells. Moreover, it was found that 70.8%, 58.2% and 48.0% respectively of MCF-7 cancer cells entered the early phase of apotosis when treated with 100 µM Que, Q3'S and Q3G for 48 h. Additionally, induction of apoptosis by Que, Q3'S and Q3G was accompanied by marginal generation of intracellular reactive oxygen species (ROS) in the MCF-7 cancer cells. Taken together, these results demonstrate that Que, Q3'S and Q3G possess strong antitumor effects through induction of ROS-dependent apoptosis pathway in MCF-7 cells.
MicroRNAs are gaining rapid attention as promising targets for cancer treatment; however, efficient delivery of therapeutic miRNA or anti-miRNA into cancer cells remains a major challenge. Our previous work identified miR-191 as an oncogenic miRNA overexpressed in breast cancer that assists in progression of malignant transformation. Thus, inhibition of miR-191 using antisense miR-191 (anti-miR-191) has immense therapeutic potential. Here, we have developed a stearylamine (SA) based cationic liposome for delivery of miR-191 inhibitor (anti-miR-191), and studied its efficacy in breast cancer cells (MCF-7 and ZR-75-1) in culture. SA liposomes alone inhibited cancer cell growth with lesser IC50s (50% inhibitory concentration) values as compared to normal mouse fibroblast cells (L929). The efficient delivery of anti-miR-191 in SA liposome complex was found to be highly effective in killing the cancer cells than a comparable dose of SA free anti-miR-191 liposome complex. The formulation also showed negligible cytotoxicity in human erythrocytes. Combined treatment of SA liposome with anti-miR-191 markedly enhanced apoptotic cell death and suppressed the migration of cancer cells in vitro. Notably, anti-miR-191 loaded SA liposome complex increased chemosensitivity of breast cancer cells to currently used anti-cancer drugs (doxorubicin or cisplatin) in free form. Our work demonstrates that anti-miR-191 loaded in SA liposome complex has promising clinical application for breast cancer therapy.
In the present work, quercetin and resveratrol, natural polyphenols with strong antioxidant and anti-inflammatory properties, were co-loaded in polymer-associated liposomes conceived for oral delivery, by exploiting the potential of pH-sensitive succinyl-chitosan. Chitosan was succinylated, characterized by Nuclear Magnetic Resonance spectroscopy and Gel Permeation Chromatography, and used to form a protective shell on the surface of liposomes. The physico-chemical properties of the succinyl-chitosan liposomes were assessed by light scattering, zeta potential, cryogenic transmission electron microscopy, and small angle X-ray scattering. Small, spherical, uni- and bilamellar vesicles were produced. The succinyl-chitosan shell increased not only the physical stability of the vesicular system, as demonstrated by accelerated stability tests, but also the release of the polyphenols to a greater extent at pH 7.0, mimicking the intestinal environment.
In this study we investigated the in vitro toxicity, impact on cell permeability and mucoadhesive potential of polymer coated liposomes intended for use in the oral cavity. A TR146 cell line was used as a model. The overall aim was to end up with a selection of safe polymer coated liposomes with promising mucoadhesive properties for drug delivery to the oral cavity. The following polymers were tested: chitosan, low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), amidated pectin (AM-pectin), Eudragit, poly(N-isopropylacrylamide-co-methacrylic acid) (p(NIPAAM-co-MAA)), hydrophobically modified hydroxyethyl cellulose (HM-HEC), and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). With chitosan as an exception, all the systems exhibited no significant effect on cell viability and permeability at the considered concentrations. Additionally, all the formulations showed to a varying degree an interaction with mucin (BSM type I-S); the positively charged formulations exhibited the strongest interaction, while the negatively and neutrally charged formulations displayed a moderate or low interaction. The ability to interact with mucin makes all the liposomal formulations promising for oromucosal administration. Although the chitosan coated liposomes affected the cell viability, this formulation also influenced the cell permeability, which makes it an interesting candidate for systemic drug delivery from the oral cavity.
Biocompatible quercetin nanovesicles were developed by coating polyethylene glycol-containing vesicles with chitosan and nutriose, aimed at targeting the colon. Uncoated and coated vesicles were prepared using hydrogenated soy phosphatidylcholine and quercetin, a potent natural anti-inflammatory and antioxidant drug. Physicochemical characterization was carried out by light scattering, cryogenic microscopy and X-ray scattering, the results showing that vesicles were predominantly multilamellar and around 130 nm in size. The in vitro release of quercetin was investigated under different pH conditions simulating the environment of the gastrointestinal tract, and confirmed that the chitosan/nutriose coating improved the gastric resistance of vesicles, making them a potential carrier system for colon delivery. The preferential localization of fluorescent vesicles in the intestine was demonstrated using the In Vivo FX PRO Imaging System. Above all, a marked amelioration of symptoms of 2,4,6-trinitrobenzenesulfonic acid-induced colitis was observed in animals treated with quercetin-loaded coated vesicles, favoring the restoration of physiological conditions. Therefore, quercetin-loaded chitosan/nutriose-coated vesicles can represent a valuable therapeutic tool for the treatment of chronic intestinal inflammatory diseases, and presumably a preventive system, due to the synergic action of antioxidant quercetin and beneficial prebiotic effects of the chitosan/nutriose complex.
Liposomes coated with polymers may have a great potential in drug delivery. In this study, adsorption of the non-ionic hydroxyethyl cellulose (HEC) onto non-charged phospholipid vesicles was investigated. Both unmodified and hydrophobically modified (HM) HEC were included in the study. Possible interactions between the liposomes and the polymers were determined by changes in the size and the size distribution. Rheo-SALS measurements were carried out to verify the successfulness of the coating process. The stability was investigated by zeta potential measurements, UV-analysis and HPTLC. Mixing unmodified HEC (Mw 90,000 and 300,000) with the liposomes yielded no increase in the particle size. HM-HEC, however, was adsorbed onto both the fluid phase egg-PC liposomes and the gel phase DPPC liposomes. The Rheo-SALS measurements confirmed the successful coating of the liposomes. Complete coating resulted in increased chemical stability of the dispersion and in addition prevented aggregation. This study has shown that the non-ionic HM-HEC can be used to form polymer coated liposomes with neutral surface charge for enhanced stability.
The present study investigated the surface coating of charged liposomes by three different types of pectin (LM, HM and amidated pectin) by particle size determinations and zeta potential measurements. The pectins and the pectin coated liposomes were visualized by atomic force microscopy. The adsorption of pectin onto positive liposomes yielded a reproducible increase in particle size and a shift of the zeta potential from positive to negative side for all three pectin types, whereas the adsorption of pectin onto negative liposomes did not render any significant changes probably due to electrostatic repulsion. The positive liposomes coated with HM-pectin gave the largest pectin coated particles with the least negative zeta potential, while the opposite was observed for the LM-pectin coated positive liposomes. Furthermore, results from dynamic light scattering revealed narrow size distributions, indicating that the degree of aggregation was low for the pectin coated liposomes. As liposomes are able to encapsulate drugs and pectin has been found to be mucoadhesive, these pectin coated liposomes may be potential drug delivery systems.
The main aim of this study was to enhance the dissolution rate of a poorly water-soluble antioxidant drug, quercetin, by fabricating its nanoparticles, complexes and solid dispersions using evaporative precipitation of nanosuspension (EPN). We studied the influence of the type of antisolvent, drug concentration and solvent to antisolvent ratio on the quercetin particles formed during EPN. With water as antisolvent, the particles were big, irregular and flake type but with benzene or hexane as antisolvent, the particles were smaller and needle type. Smallest particles of 220 nm diameter were achieved with hexane as antisolvent, lowest drug concentration and highest solvent to antisolvent ratio. The relative dissolution values showed that the dissolution rate of the EPN prepared quercetin nanoparticles was much higher than that of the raw drug. Quercetin formed inclusion complexes with β-cyclodextrin, and solid dispersions with polyvinylpyrrolidone and pluronic F127, where quercetin was present in an amorphous form and/or was dispersed at a molecular level. The dissolution rate of quercetin in its complexes and solid dispersions improved significantly from the raw quercetin as indicated by the percent dissolution efficiency. It was interesting to note that at lower carrier concentration, the solid dispersions of quercetin with polyvinylpyrrolidone and pluronic F127 presented better dissolution than its complex with β-cyclodextrin but at higher carrier concentration, there was no significant difference in the dissolution behavior of the three formulations. Using Korsmeyer-Peppas model, diffusion was found to be the main release mechanism.
In the present study the evaporative precipitation into aqueous solution (EPAS) process and the high homogenization press (HPH) process were compared to evaluate their feasibility to form a chemically stable quercetin nanosuspension. The particle size and Zeta potential of the EPAS nanosuspension were similar to those of the HPH nanosuspension. Differences in results of differential scanning calorimetery and X-ray measures were observed between the two processes. The crystalline-to-amorphous phase transition was shown in the profile of EPAS dried powder. On the contrary the initial crystalline state of drug was maintained throughout the HPH process. Dissolution test results indicated that the EPAS process showed a higher improvement in the drug solubility and dissolution rate than the HPH process. At last the high performance liquid chromatography (HPLC) analysis proved the superiority of both nanosuspensions over QCT solution formulation for the chemical and photo-stability. As a result, it can be concluded that the EPAS and HPH techniques were feasible to prepare a chemically stable QCT nanosuspension with significantly enhanced dissolution rate.
Liposomes have been coated with the pH responsive polymer, Eudragit S100, and the formulation's potential for lower gastrointestinal (GI) targeting following oral administration assessed. Cationic liposomes were coated with the anionic polymer through simple mixing. The evolution of a polymer coat was studied using zeta potential measurements and laser diffraction size analysis. Further evidence of an association between polymer and liposome was obtained using light and cryo scanning electron microscopy. Drug release studies were carried out at pH 1.4, pH 6.3 and pH 7.8, representing the pH conditions of the stomach, small intestine and ileocaecal junction, respectively. The polymer significantly reduced liposomal drug release at pH 1.4 and pH 6.3 but drug release was equivalent to the uncoated control at pH 7.8, indicating that the formulation displayed appropriate pH responsive release characteristics. While the coating layer was not able to withstand the additional challenge of bile salts this reinforces the importance of evaluating these types of formulations in more complex media.
A new microemulsion system has been developed to increase the solubility and oral absorption of quercetin, a poorly water-soluble drug. The formulation of quercetin-loaded microemulsion was optimized by a simplex lattice experiment design. The optimized microemulsion formulation consisted of oil (7%, w/w), surfactant (48%, w/w), and cosurfactant (45%, w/w). Under this condition, the mean droplet diameter of microemulsion was 38.9 nm and solubility of quercetin in the microemulsion was 4.138 mg/ml. The in situ absorption property of quercetin-loaded microemulsion in rat intestine was studied and the results showed there was significant difference in absorption parameters such as K(a), t(1/2) and uptake percentages between microemulsion and micelle solution containing quercetin. The study on absorption percentage in different regions of rat intestine attested that the colon had the best permeability, followed by ileum, duodenum in order. It can be concluded that microemulsion can improve the solubility and oral absorption of quercetin, a poorly water-soluble drug.
The aim of the present study is to design and characterize quercetin-loaded solid lipid nanoparticles (QT-SLNs), clarify the absorption mechanism of QT-SLNs and to evaluate the potential of using solid lipid nanoparticles (SLNs) as an oral delivery carrier for poorly water soluble drugs. QT-SLNs were prepared by an emulsification and low-temperature solidification method. The QT-SLNs presented as spherically shaped under transmission electron microscopy, with an average diameter of 155.3 nm. The average drug entrapment efficiency, drug loading and zeta potential were 91.1%, 13.2% and -32.2 mV, respectively. Drug release from QT-SLNs was fitted to a double phase kinetics model and the equation was as follows: 100-Q=98.87e(-0.1042t)+42.45e(-0.0258t). The absorption of QT-SLNs in the gastrointestinal (GI) tract was studied using an in situ perfusion method in rats. It was found that the absorption percent in the stomach for 2 h was only 6.20%, the absorption process of intestine was first-process with passive diffusion mechanism, and the main absorptive segments were ileum and colon. A pharmacokinetic study was conducted in rats after oral administration of quercetin at 50 mg/kg in the form of either QT-SLNs or suspension. The plasma concentration-time curves were both fitted to a one-compartment model. The relative bioavailability of QT-SLNs to quercetin suspension was 571.4%. The T(max) and MRT for quercetin in plasma were both delayed. Our studies provide evidence that SLNs are valuable as an oral delivery carrier to enhance the absorption of a poorly water soluble drug, quercetin.
The characteristics of the adsorption process of hydroxypropylmethylcellulose (HPMC) of molecular weight 35400 Da and nominal viscosity 100 cps onto liposomes prepared with different egg lecithin-cholesterol molar ratios were examined. Adsorption isotherms were constructed and analysed to investigate the mechanisms implicated in the incorporation of the polymer to the interface. Only the isotherms obtained with cholesterol-free liposomes were fitted with Langmuir model. When cholesterol is present in the composition they present a sigmoidal slope. The mechanism of adsorption depends on liposome composition being the main force that drives polymer adsorption of hydrophobic nature. The apparent volumes of HPMC indicate that the conformation of the adsorbed macromolecules depends on liposome composition. Hydration enthalpy values show that adsorbed polymers do not give more hydrophilic systems after freeze-drying as expected with the hydrophilic characteristics of the HPMC.
Cationic liposomes are expected to be useful as nonviral vectors for gene delivery. Cationic liposomes showed cytotoxicity, and we proposed that the cytotoxicity is through apoptosis. In this study, we examined the effects of liposomal properties, such as liposomal charge, size, membrane fluidity, and PEG coating, on the induction of apoptosis in the macrophage-like cell line RAW264.7.
RAW264.7 cells were treated with liposomes, and the induction of apoptosis was evaluated by monitoring the changes in DNA content by flow cytometry. The association of liposomes with cells and the generation of reactive oxygen species (ROS) were also measured by flow cytometry.
The induction of apoptosis of RAW264.7 cells was dependent on the concentrations of stearylamine or cholesterol, a component of cationic liposomes. A significant correlation was observed between the degree of apoptosis and association of cationic liposomes with the cells. Coating the liposomal surface with polyethylene glycol (PEG) decreased the association of cationic liposomes with RAW264.7 cells and reduced the induction of apoptosis. Liposomal size also affected the induction of apoptosis, and larger liposomes showed a higher degree of apoptosis induction. Furthermore, ROS, which were required for the induction of apoptosis by cationic liposomes, were generated in a cholesterol content-dependent manner, and ROS generation was also decreased by PEG coating as the association and the induction of apoptosis were reduced.
The degree of apoptosis is related to the extent of association of cationic liposomes with cells and is related to the generation of ROS.
In this paper we extend our previous experimental work on interaction between polyelectrolytes and liposomes. First, the adsorption of chitosan and alkylated chitosan (cationic polyelectrolytes) with different alkyl chain lengths on lipid membranes of liposomes is examined. The amount of both chitosans adsorbed remains the same even if more alkylated polysaccharide has to be added to get saturation if compared with unmodified chitosan. It is demonstrated that alkyl chains do not specifically interact with the lipid bilayer and that electrostatic interaction mechanism governs the chitosan adsorption. The difference observed between unmodified and alkylated chitosans behavior to reach the plateau can be interpreted in terms of a competition between electrostatic polyelectrolyte adsorption on lipid bilayer and hydrophobic autoassociation in solution (which depends on the alkyl chain length). Second, interaction of liposomes with hyaluronan (HA) and alkylated hyaluronan (anionic polyelectrolytes) is analyzed. The same types of results as discussed for chitosan are obtained, but in this case, autoassociation of alkylated HA only occurs in the presence of salt excess. Finally, a first positive layer of chitosan is adsorbed on the lipid membrane, followed by a second negative layer of HA at three different pHs. This kind of multilayer decoration allows the control of the net charge of the composite vesicles. A general conclusion is that whatever the pH and, consequently, the initial charge of the liposomes, chitosan adsorption gives positively charged composite systems, which upon addition of hyaluronan, give rise to negatively charged composite vesicles.