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Particle size and morphology of DP loaded microspheres (a-c are microscope images for Formulation A-C, respectively. The magnification time was 10 × 10, one units represent 23 m; d was particle size distribution of fomulation C; e and f was SEM image of formulation C under a different view).
Source publication
The purpose of this study was to develop a PLGA microspheres-based donepezil (DP) formulation which was expected to sustain release of DP for one week with high encapsulation efficiency (EE). DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method. The optimized formulation which...
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Citations
... Furthermore, MS can protect drugs from chemical degradation and transformation, thereby improving the drug stability. 43,44 Especially the biocompatible and biodegradable poly(lactic-co-glycolic-acid) (PLGA) material has been widely used. Nowadays, intratumoral delivery of MS results in high drug concentration in tumors, minor leakage in plasma, and good therapeutic effect. ...
Research for tumor treatment with significant therapy effects and minimal side-effects has been widely carried over the past few decades. Different drug forms have received a lot of attention. However, systemic biodistribution induces efficacy and safety issues. Intratumoral delivery of agents might overcome these problems because of its abundant tumor accumulation and retention, thereby reducing side effects. Delivering hydrogels, nanoparticles, microneedles, and microspheres drug carriers directly to tumors can realize not only targeted tumor therapy but also low side-effects. Furthermore, intratumoral administration has been integrated with treatment strategies such as chemotherapy, enhancing radiotherapy, immunotherapy, phototherapy, magnetic fluid hyperthermia, and multimodal therapy. Some of these strategies are ongoing clinical trials or applied clinically. However, many barriers hinder it from being an ideal and widely used option, such as decreased drug penetration impeded by collagen fibers of a tumor, drug squeezed out by high density and high pressure, mature intratumoral injection technique. In this review, we systematically discuss intratumoral delivery of different drug carriers and current development of intratumoral therapy strategies.
... D/Max-BR diffractometer (Rigaku, Tokyo, Japan) with Cu Kα radiation was used to analyze the structure and crystalline forms of the fiber contents. Analyses were conducted at 40 mV and 30 mA over the 2θ range of 5-80° [32][33][34][35][36] at a rate of 2°/min. OriginPro 7.0 software (OriginLab Corporation, MA, USA) was used to convert data to diffractograms for evaluation. ...
... This drug was chosen to assess the ability of the synthesized materials to bind to a drug and deliver it to the brain, and to enable comparisons between groups of animals treated with the nanomaterials and the control group (treated with free donepezil). Furthermore, a sustained release of donepezil may benefit patients with Alzheimer's disease, as it may be challenging for these patients to adhere to scheduled self-medication [22,23]. In addition, donepezil can also have gastrointestinal side effects (e.g., diarrhea, J Mater Sci nausea, anorexia, and muscle seizures), and a nonoral administration via can also bring benefits to the patients [23]. ...
Molecularly imprinted polymers (MIPs) have a high potential for use as drug delivery carriers. These materials exhibit beneficial properties such as stability, low toxicity, biodegradability, and the ability to form specific binding sites. New systems capable of crossing the blood–brain barrier (BBB) are important for the development of new treatments for nervous central system diseases. Due to the presence of apolipoprotein E (ApoE) receptors in the BBB, some nanomaterials functionalized with ApoE may be efficient systems for the drug delivery in the brain. In this way, a nano-MIP conjugated with ApoE (MIP-ApoE) was synthesized, characterized and evaluated as a possible drug nanocarrier to the brain. A non-imprinted polymer (NIPs) and a NIP conjugated with ApoE (NIP-ApoE) were also synthesized and compared with MIP and MIP-ApoE. The nanoparticles were loaded with donepezil (drug used for a proof-of-principle study), and the formulations were tested for cytocompatibility, in vitro release, and permeability through BBB model using hCMEC/D3 cells. Free donepezil, donepezil-loaded nanoparticles, and unloaded nanoparticles had a hemolytic activity lower than 15% and cell viability greater than 70%. The quantified donepezil in the plasma samples of animals treated with MIP and MIP-ApoE supported the in vitro results of sustainable donepezil release by these nanoparticles. When the nanoparticles were functionalized with ApoE, the permeability in the hCMEC/D3 monolayer increased (1.9 times). The brain samples of animals treated with MIP-ApoE had a slightly lower concentration of donepezil than the MIP treatment. One possible explanation is that, only the MIP-ApoE, with part of the donepezil complexed at its binding sites, can penetrate the brain. As a result, a reduced amount of donepezil remains free to be quantified.
Graphical Abstract
... Marketed PLGA based depot formulations include in-situ gel-forming implants, implants, and microparticles [18]. Among these formulations, microparticles are the most convenient formulation with respect to ease of administration and non-invasive method of administration [18,21,22]. Currently, researchers are working on the development of a continuous process of scale-up for the production of PLGA MS by in-line homogenizer approach, which is a technique used for the improvement of the batch-to-batch variability observed during the preparation of PLGA MS using conventional methods [23,24]. ...
The Human Immunodeficiency Virus (HIV) continues to be a major global health issue, with 38.4 million people infected at the end of 2021. The daily dosage regimen of Anti-retroviral (ARV) treatment leads to poor treatment adherence and patients’ non-compliance. Tenofovir and its prodrugs, such as Tenofovir alafenamide (TAF) are generally used for the Pre-Exposure Prophylaxis (PrEP) of HIV. The current work focusses on the development of long- acting TAF loaded Poly-Lactic-co-Glycolic Acid (PLGA) Microspheres (MS) to improve the treatment adherence and patient compliance. MS were formulated using the industrially scalable in-line homogenizer approach using the solid-in-oil-in-water (S/O/W) emulsion solvent evaporation method. The surface morphology study carried out by SEM indicated the formation of dense, non-porous and spherical MS. The Differential Scanning Calorimetry (DSC) and X-ray Diffractometry (XRD) study revealed the formation of an amorphous form of TAF in the MS. The in vitro release study indicated the lower initial burst release of TAF and sustained release of TAF up to 15 days from the MS. The cytotoxicity and HIV inhibitory studies in the reporter TZM-bl cell line with different HIV-1 strains indicated the safety and effectiveness of TAF loaded PLGA MS. Thus, the long-acting MS would be a better alternative as a PrEP measure for HIV infection.
... Bazı çalışmalarda, örnek alımından sonra salım ortamı ve nanopartiküler sistemler arasında fiziksel ayrımı sağlamak için ayırma yöntemi olarak polimerik malzemeleri süzebilen uygun gözenek boyutuna sahip membran filtreler kullanılarak filtrasyon gerçekleştirilmiştir [41, 59,60]. Ayrıca, nanopartiküler sistemlerin küçük boyutları nedeniyle santrifüjleme, ultrasantrifüjleme, ultrafiltrasyon ve basınçlı ultrafiltrasyon gibi yüksek enerjili ayırma tekniklerinin sıklıkla uygulandığı da görülmektedir [59,61]. Belirli zaman noktalarında salım ortamından alınan örneklerde nanopartiküler sistem ile salım ortamını ayırmak için kullanılan santrifüjleme işlemi, yüksek enerjili ayırma teknikleri arasında en popüler yöntemdir. ...
Bir ilacın dozaj şeklinden salım özelliklerinin incelenmesinde kullanılan in vitro salım testi sayesinde hem ilacın in vitro yararlanımı hakkında bilgi edinilmesi hem de diğer ürünlerle eşdeğerliğinin karşılaştırması mümkün olmaktadır. Doğru ve güvenilir sonuçlar elde edilmesi için uygun salım testi yönteminin ve uygun salım koşullarının (sıcaklık, salım ortamı, pH, karıştırma /akış hızı vb.) seçilmesi esastır. Farmakopelerde birçok dozaj şekli için in vitro salım testi yöntemleri ve koşulları tanımlanmış olmasına karşın hâlihazırda nanopartiküler ilaç taşıyıcı sistemler için bir test yöntemi farmakopelerde mevcut değildir. Bu derlemede, nanopartiküler sistemlerden ilaç salımının incelenmesinde kullanılan test yöntemleri (örnek alma ve ayırma, membran difüzyon, sürekli akış vb.) ve güncel uygulamalarından bahsedilecek ve birbirlerine olan üstünlükleri ve sakıncaları tartışılacaktır.
... Table 2 shows that the values of R 2 for First-order kinetic model (R 2 > 0.99) was higher than other models, indicating it was the most suitable model for the sustained release behavior of CEO and CEO-SNP. This meant that the release of CEO and CEO-SNP was driven by the concentration gradient [46]. Table 2. ...
... Table 2 shows that the values of R 2 for First-order kinetic model (R 2 > 0.99) was higher than other models, indicating it was the most suitable model for the sustained release behavior of CEO and CEO−SNP. This meant that the release of CEO and CEO−SNP was driven by the concentration gradient [46]. ...
To improve the sustained release and long-term antibacterial activity of Chimonanthus nitens Oliv. essential oil (CEO), novel sponge-liked nanoporous silica particles (SNP) were synthesized via the soft template method, which was employed as a biocompatible carrier to prepare spong-liked nanoporous silica particles loading with CEO (CEO-SNP) through physical adsorption. The structure and properties of the samples were characterized via N2 adsorption/desorption measurements, thermogravimetry (TGA), Fourier transform infrared, SEM and TEM. The result showed that the SNP exhibited an excellent loading capability of CEO up to 76.3%. The thermal stability and release behavior of the CEO were significantly improved via the physical adsorption of the SNP materials. The release profile of CEO was in accordance with the first-order kinetic model, which meant that the release mechanism was drug Fick’s diffusion. The antibacterial evaluation results demonstrated that the CEO-SNP exhibited strong antibacterial activity against S. aureus, E. coli and P. aeruginosa. The antibacterial results have shown that the CEO-SNP could destroy the cell structure of bacteria, and result in the generation of oxidative stress and the release of nucleic acid. After storage of 30 d at 25 °C, the CEO-SNP still had the stronger antibacterial activity towards S. aureus, E. coli and P. aeruginosa in comparison with CEO. Therefore, the sponge-like silica nanoporous particles seemed to be a promising carrier for long-term stability and antibacterial delivery of CEO.
... The TGA and DTG curves of DH and NFencapsulated ZIF-8 incorporating CS and BCD were shown in Fig. 4e,f. According to the thermogram, the first stage of thermal degradation of donepezil drug was observed between 87-88°C [36]. The CS incorporated ZIF-8 showed a weight loss between 200-600°C at 284°C and 249°C for DH@ZIF-8/CS and NF@ZIF-8/CS, respectively, corresponding to the process of organic linkage ligand degradation in ZIF-8 [37] and CS degradation [38] in the nanoparticles. ...
... Many advanced nano-based technologies have been highlighted to improve the brain-targeting drug delivery for the treatment of AD. Nano-based formulations are capable of increasing drug plasma concentrations and their small particle size, surface charge and surfactants facilitates particle passage across BBB tight junctions via r various transcytosis mechanisms, [8,9]. Amongst these advances, lipid-based nanoformulations acquired more attention from the researcher for the brain targeting drug delivery with additional solubility and stability potential. ...
Purpose
Asiatic acid (AA) is reported for its neuroprotective potential in Alzheimer’s disease (AD). This present work aimed to develop AA loaded nanostructured lipid carriers (AAN) for targeting the delivery of AA into the brain and ameliorating the cognitive deficits in AD rats.
Methods
AAN was optimized using the Box-Behnken design, considering 3 factors (soya lecithin, tween 80, and high pressure homogenizer (HPH) pressure) as independent variables while particle size (PS), zeta potential (ZP) and entrapment efficiency (EE) were dependent variables. Cytotoxicity assay and internalization studies of AAN were evaluated in SH-SY5Y cells and further neuroprotective efficiency on intracellular amyloid beta (Aβ) aggregation was evaluated in Aβ 1–42 treated cells with thioflavin T (ThT). The behavioral acquisition effects were evaluated in Aβ 1–42 (5 µg/ 5 µL, intracerebroventricular (ICV), unilateral) induced AD model followed by the histology and quantification of neurotransmitters levels.
Results
The optimized AAN revealed desired PS (44.1 ± 12.4 nm), ZP (- 47.1 ± 0.017 mv) and EE (73.41 ± 2.53%) for brain targeting delivery of AA. In-vitro, AAN exhibited better neuroprotective potential than AA suspension (AAS). AA content was 1.28 folds and 2.99 folds heightened in plasma and brain respectively after the i.p. administration of AAN as compared to AAS. The results of pharmacodynamic studies manifested the AAN treatment significantly (p < 0.05) ameliorated the cognitive deficits.
Conclusions
Hence, developed AAN has neuroprotective potential and should be further considered as an unconventional platform in preclinical model for the management of AD.
Graphical Abstract
... The researchers have found different ways to overcome this problem; (a) using a free base instead of the salt form of the drug. 40 (b) Conformational rigidification or hydrophobization using polyelectrolytes. 41 (c) By adding salts such as NaCl, NaBr to the external aqueous phase. ...
Introduction: Glatiramer acetate (GA) is a newly emerged therapeutic peptide to reduce the frequency of relapses in multiple sclerosis (MS). Despite its good performance in controlling MS, it is not widely used due to daily or biweekly subcutaneous injections due to rapid degradation and body clearance. Therefore, implant design with sustained release leads to prolonged biological effects by gradually increasing drug exposure and protecting GA from rapid local degradation.
Methods: Different emulsion methods, PLGA type, surfactant concentration, drug/polymer ratio, drying processes, stirring method, and other variables in preliminary studies modified the final formulation. The release kinetics were studied through mechanistic kinetic models such as zero-order, Weibull, Higuchi, etc. In this study, all challenges for easy scale-up, methodological detail, and a simple, feasible setup in mass production were discussed.
Results: The optimized formulation was obtained by 1:6 drug/PLGA, 0.5% w/w polyvinyl alcohol, and 0.75% w/w NaCl in the external aqueous phase, 1:10 continuous phase to dispersed phase ratio, and without any surfactant in the primary emulsion. The final freeze-dried particles presented a narrow distributed size of 1-10 µm with 7.29% ± 0.51 drug loading and zero-order release behavior with appropriate regression correlation (R2 98.7), complete release, and only 7.1% initial burst release.
Conclusion: Therefore, to achieve improvement in patient compliance through better and longer efficacy, designing the parenteral sustained release microspheres (MPSs) of this immune modulator is a promising approach that should be considered.
... The drug loading and encapsulation efficiency of the KSL-W@PLGA microspheres were calculated by using the UV spectrophotometer and the calibration curve of KSL-W measured above [23]. The specific operation method was as follows: ...
Objectives
To investigate the feasibility of the 3D printed scaffold for periapical bone defects.
Methods
In this study, antimicrobial peptide KSL-W-loaded PLGA sustainable-release microspheres (KSL-W@PLGA) were firstly prepared followed by assessing the drug release behavior and bacteriostatic ability against Enterococcus faecalis and Porphyromonas gingivalis . After that, we demonstrated that KSL-W@PLGA/collagen (COL)/silk fibroin (SF)/nano-hydroxyapatite (nHA) (COL/SF/nHA) scaffold via 3D-printing technique exhibited significantly good biocompatibility and osteoconductive property. The scaffold was characterized as to pore size, porosity, water absorption expansion rate and mechanical properties. Moreover, MC3T3-E1 cells were seeded into sterile scaffold materials and investigated by CCK-8, SEM and HE staining. In the animal experiment section, we constructed bone defect models of the mandible and evaluated its effect on bone formation. The Japanese white rabbits were killed at 1 and 2 months after surgery, the cone beam computerized tomography (CBCT) and micro-CT scanning, as well as HE and Masson staining analysis were performed on the samples of the operation area, respectively. Data analysis was done using ANOVA and LSD tests. (α = 0.05).
Results
We observed that the KSL-W@PLGA sustainable-release microspheres prepared in the experiment were uniform in morphology and could gradually release the antimicrobial peptide (KSL-W), which had a long-term antibacterial effect for at least up to 10 days. HE staining and SEM showed that the scaffold had good biocompatibility, which was conducive to the adhesion and proliferation of MC3T3-E1 cells. The porosity and water absorption of the scaffold were (81.96 ± 1.83)% and (458.29 ± 29.79)%, respectively. Histological and radiographic studies showed that the bone healing efficacy of the scaffold was satisfactory.
Conclusions
The KSL-W@PLGA/COL/SF/nHA scaffold possessed good biocompatibility and bone repairing ability, and had potential applications in repairing infected bone defects.
Clinical significance The 3D printed scaffold not only has an antibacterial effect, but can also promote bone tissue formation, which provides an alternative therapy option in apical periodontitis.
