poly(D,L-lactic-co-glycolic) Acid Research Articles

Development of BDNF/NGF/IKVAV Peptide Modified and Gold Nanoparticle Conductive PCL/PLGA Nerve Guidance Conduit for Regeneration of the Rat Spinal Cord Injury.

Spinal cord injuries are very common worldwide, leading to permanent nerve function loss with devastating effects in the affected patients. The challenges and inadequate results in the current clinical treatments are leading scientists to innovative neural regenerative research. Advances in nanoscience and neural tissue engineering have opened new avenues for spinal cord injury (SCI) treatment. In order for designed nerve guidance conduit (NGC) to be functionally useful, it must have ideal scaffold properties and topographic features that promote the linear orientation of damaged axons. In this study, it is aimed to develop channeled polycaprolactone (PCL)/Poly-D,L-lactic-co-glycolic acid (PLGA) hybrid film scaffolds, modify their surfaces by IKVAV pentapeptide/gold nanoparticles (AuNPs) or polypyrrole (PPy) and investigate the behavior of motor neurons on the designed scaffold surfaces in vitro under static/bioreactor conditions. Their potential to promote neural regeneration after implantation into the rat SCI by shaping the film scaffolds modified with neural factors into a tubular form is also examined. It is shown that channeled groups decorated with AuNPs highly promote neurite orientation under bioreactor conditions and also the developed optimal NGC (PCL/PLGA G1-IKVAV/BDNF/NGF-AuNP50 ) highly regenerates SCI. The results indicate that the designed scaffold can be an ideal candidate for spinal cord regeneration.

DEVELOPMENT AND OPTIMIZATION OF POLYMERIC NANOPARTICLES OF GLYCYRRHIZIN: PHYSICOCHEMICAL CHARACTERIZATION AND ANTIOXIDANT ACTIVITY

Objective: The aim of the present study to develop, optimize and characterize Poly (D, L-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) loaded with isolated Glycyrrhizin (Glyc) and investigate for antioxidant activity. Methods: PLGA nanoparticles loaded with Glycyrrhizin were synthesized by an adapted emulsion-evaporation method. Nanoparticles were evaluated for particle size, entrapment efficiency and Polydispersiblity index (PDI). Further, Box Benkhen design was applied for optimization of the formulation parameters and the effect of three independent variables such as PLGA concentration, amount of glycyrrhizin, polyvinyl alcohol (PVA) concentration on particle size, polydispersiblity index and the entrapment efficiency (response variables) were investigated. The antioxidant capacity of optimized nanoparticle formulation loaded with glycyrrhizin was compared with free glycyrrhizin by DPPH assay. Results: The particle size, entrapment efficiency and PDI of optimized Glyc-NPs was found to be 144.20 nm, 68.0% and 0.315 respectively. Optimized Glyc-NPs showed sustained release of drug 79.06% in 48 hours with improved free radical scavenging activity than isolated Glycyrrhizin. Conclusion: PLGA nanoparticles were found to be suitable carrier for Glycyrrhizin at lower levels than originally required for enhanced functional properties.

Encapsulation of Neem oil from Azadirachta indica into Poly (lactic-co-glycolic acid) as a novel sprayable miticide system with long-term storage stability and controlled release kinetic

In this study, Neem oil (NO) was extracted from the seeds of Azadirachta indica as a natural miticide agent. To prolong the insecticidal activity and control the sustainable release, various concentrations of NO were encapsulated in poly(D, L-lactic-co-glycolic) acid (PLGA) copolymers and high and low molecular weight (Mw) polyvinyl alcohol (PVAH and PVAL) microparticles (MPs) using the single and double emulsion solvent evaporation method. The effects of different parameters, such as the molecular weight of the stabilizing agent (PVA), stirring time, and polymer concentrations, on the size, stability, morphology, encapsulation efficiency, and release kinetics of the MPs were investigated. The presence of NO in PLGA/PVA MPs was confirmed by a shift in the glass transition temperature (Tg) to lower temperatures in the DSC thermograph, the appearance of peaks at 2854 cm−1 in the FTIR spectrum, a peak at 205 nm in the UV–vis spectrum and a rough surface in SEM. Moreover, the release kinetics of the MPs demonstrated sustained release of NO over 48 h. In terms of MPs storage, temperature affected short-term stability, while long-term stability after one year in a dark environment at room temperature was confirmed by the particles' strength. The miticide assay on dust mites Dermatophagoides pteronyssinus revealed that MPs with the highest NO concentration (PLGA/PVAL/NO 65%) exhibited the most effective miticidal activity, achieving a 100% kill rate after 24 h. Finally, the colloidal dispersion and stability of the MPs over time were assessed using rheology, and the results confirmed the particles' spray ability for miticide application.

Design of IKVAV peptide/gold nanoparticle decorated, micro/nano-channeled PCL/PLGA film scaffolds for neuronal differentiation and neurite outgrowth

In the field of neural tissue engineering, intensive efforts are being made to develop tissue scaffolds that can support an effective functional recovery and neural development by guiding damaged axons and neurites. Micro/nano-channeled conductive biomaterials are considered a promising approach for repairing the injured neural tissues. Many studies have demonstrated that the micro/nano-channels and aligned nanofibers could guide the neurites to extend along the direction of alignment. However, an ideal biocompatible scaffold containing conductive arrays that could promote effective neural stem cell differentiation and development, and also stimulate high neurite guidance has not been fully developed. In the current study, we aimed to fabricate micro/nano-channeled polycaprolactone (PCL)/Poly-d,l-lactic-co-glycolic acid (PLGA) hybrid film scaffolds, decorate their surfaces with IKVAV pentapeptide/gold nanoparticles (AuNPs), and investigate the behavior of PC12 cells and neural stem cells (NSCs) on the developed biomaterial under static/bioreactor conditions. Here we show that channeled groups decorated with AuNPs highly promote neurite outgrowth and neuronal differentiation along linear lines in the presence of electrical stimulation, compared with the polypyrrole (PPy) coating, which has been used traditionally for many years. Hopefully, this newly developed channeled scaffold structure (PCL/PLGA-AuNPs-IKVAV) could help to support long-distance axonal regeneration and neuronal development after different neural damages.

Therapeutic Delivery of Tumor Suppressor miRNAs for Breast Cancer Treatment.

The death rate from breast cancer (BC) has dropped due to early detection and sophisticated therapeutic options, yet drug resistance and relapse remain barriers to effective, systematic treatment. Multiple mechanisms underlying miRNAs appear crucial in practically every aspect of cancer progression, including carcinogenesis, metastasis, and drug resistance, as evidenced by the elucidation of drug resistance. Non-coding RNAs called microRNAs (miRNAs) attach to complementary messenger RNAs and degrade them to inhibit the expression and translation to proteins. Evidence suggests that miRNAs play a vital role in developing numerous diseases, including cancer. They affect genes critical for cellular differentiation, proliferation, apoptosis, and metabolism. Recently studies have demonstrated that miRNAs serve as valuable biomarkers for BC. The contrast in the expression of miRNAs in normal tissue cells and tumors suggest that miRNAs are involved in breast cancer. The important aspect behind cancer etiology is the deregulation of miRNAs that can specifically influence cellular physiology. The main objective of this review is to emphasize the role and therapeutic capacity of tumor suppressor miRNAs in BC and the advancement in the delivery system that can deliver miRNAs specifically to cancerous cells. Various approaches are used to deliver these miRNAs to the cancer cells with the help of carrier molecules, like nanoparticles, poly D, L-lactic-co-glycolic acid (PLGA) particles, PEI polymers, modified extracellular vesicles, dendrimers, and liposomes. Additionally, we discuss advanced strategies of TS miRNA delivery techniques such as viral delivery, self-assembled RNA-triple-helix hydrogel drug delivery systems, and hyaluronic acid/protamine sulfate inter-polyelectrolyte complexes. Subsequently, we discuss challenges and prospects on TS miRNA therapeutic delivery in BC management so that miRNAs will become a routine technique in developing individualized patient profiles.

Coating of chitosan on poly D,L-lactic-co-glycolic acid thymoquinone nanoparticles enhances the anti-tumor activity in triple-negative breast cancer.

Breast cancer is the second most common cancer around the world. Triple-negative breast cancer (TNBC) is characterized by the absence of three receptors: progesterone, estrogen, and human epidermal growth factor-2 receptor (HER2). Various synthetic chemotherapies have gained attention but they caused unwanted side effects. Therefore, some secondary therapies are now becoming famous against this disease. For instance, natural compounds have been extensively researched against many diseases. However, enzymatic degradation and low solubility remain a major concern. To combat these issues, various nanoparticles have been synthesized and optimized from time to time, which increases its solubility and hence therapeutic potential of a particular drug increases. In this study, we have synthesized Poly D,L-lactic-co-glycolic acid (PLGA) loaded thymoquinone (TQ) nanoparticle (PLGA-TQ-NPs) and then coated them by chitosan (CS) (PLGA-CS-TQ-NPs), which was characterized by different methods. Size of non-coated NPs was 105nm with PDI value of 0.3 and the size of coated NPs was 125nm with PDI value of 0.4. Encapsulation efficiency (EE%) and Drug loading (DL%) was found to be 70.5 ± 2.33 and 3.38 for non-coated and 82.3 ± 3.11 and 2.66 for coated NPs respectively. We have also analysed their cell viability against MDA-MB-231 and SUM-149 TNBC cell lines. The resultant, nanoformulations exhibit anti-cancerous activity in a dose and time-dependent manner for MDA-MB-231 and SUM-149 cell lines with an IC50 value of (10.31 ± 1.15, 15.60 ± 1.25, 28.01 ± 1.24) and (23.54 ± 1.24, 22.37 ± 1.25, 35 ± 1.27) for TQ free, PLGA-TQ-NPs and PLGA-CS-TQ-NPs respectively. For the first time, we have developed a nanoformulations of PLGA loaded TQ coated with CS NPs (PLGA-CS-TQ-NPs) against TNBC which led to their enhanced anti-cancerous effects.

Application of PLGA as a Biodegradable and Biocompatible Polymer for Pulmonary Delivery of Drugs

Pulmonary administration of biodegradable polymeric formulation is beneficial in the treatment of various respiratory diseases. For respiratory delivery, the polymer must be non-toxic, biodegradable, biocompatible, and stable. Poly D, L-lactic-co-glycolic acid (PLGA) is a widely used polymer for inhalable formulations because of its attractive mechanical and processing characteristics which give great opportunities to pharmaceutical industries to formulate novel inhalable products. PLGA has many pharmaceutical applications and its biocompatible nature produces non-toxic degradation products. The degradation of PLGA takes place through the non-enzymatic hydrolytic breakdown of ester bonds to produce free lactic acid and glycolic acid. The biodegradation products of PLGA are eliminated in the form of carbon dioxide (CO2) and water (H2O) by the Krebs cycle. The biocompatible properties of PLGA are investigated in various in vivo and in vitro studies. The high structural integrity of PLGA particles provides better stability, excellent drug loading, and sustained drug release. This review provides detailed information about PLGA as an inhalable grade polymer, its synthesis, advantages, physicochemical properties, biodegradability, and biocompatible characteristics. The important formulation aspects that must be considered during the manufacturing of inhalable PLGA formulations and the toxicity of PLGA in the lungs are also discussed in this paper. Additionally, a thorough overview is given on the application of PLGA as a particulate carrier in the treatment of major respiratory diseases, such as cystic fibrosis, lung cancer, tuberculosis, asthma, and pulmonary hypertension.

Oral vaccination for sustainable disease prevention in aquaculture-an encapsulation approach.

The prevalence of infectious diseases in the aquaculture industry and a limited number of safe and effective oral vaccines has imposed a challenge not only for fish immunity but also a threat to human health. The availability of fish oral vaccines has expanded recently, but little is known about how well they work and how they affect the immune system. The unsatisfactory efficacy of existing oral vaccinations is partly attributable to the antigen degradation in the adverse gastrointestinal environment of fishes, the highly tolerogenic gut environment, and inferior vaccine formulation. To overcome such challenges in designing: an easier, cost-efficient, and effective vaccination method, several encapsulation methods are being adopted to safeguard antigens from the intestinal atmosphere for their immunogenic functions. Oral vaccination is easily degraded by gastric acids and enzymes before reaching the immunological site; however, this issue can be solved by encapsulating antigens in poly-biodegradable nanoparticles, transgenic designed bacteria, plant systems, and live feeds. To enhance the immunological impact, each antigen delivery method operates at a different level. Utilizing nanotechnology, it has been possible to regulate vaccination parameters, target particular cells, and lower the antigen dosage with potent nanomaterials such as chitosan, poly D,L-lactic-co-glycolic acid (PLGA) as vaccine carriers. Live feeds such as Artemia salina can be utilized as bio-carrier, owing to their appropriate size and non-filter feed system, through a process called bio-encapsulation. It ensures the protection of antigens over the fish intestine and ensures complete uptake by immune cells in the hindgut for increased immune response. This review comprises recent advances in oral vaccination in aquaculture in terms of an encapsulation approach that can aid in future research.

Construction of a Stimuli-Responsive DNAzyme-Braked DNA Nanomachine for the Amplified Imaging of miRNAs in Living Cells and Mice

Construction of a Stimuli-Responsive DNAzyme-Braked DNA Nanomachine for the Amplified Imaging of miRNAs in Living Cells and Mice

Validation of a Rapid and Easy-to-Apply Method to Simultaneously Quantify Co-Loaded Dexamethasone and Melatonin PLGA Microspheres by HPLC-UV: Encapsulation Efficiency and In Vitro Release.

This paper discusses the development and validation of a rapid method for the reversed phase HPLC-UV quantification of biodegradable poly(D,L-lactic-co-glycolic) acid (PLGA) microspheres co-loaded with two neuroprotective agents (dexamethasone and melatonin) (DX-MEL-MSs) to be intravitreally administered as a promising glaucoma treatment. The study was performed to validate two procedures that quantify the content of the two active substances entrapped into the polymer matrix during an encapsulation efficiency assay and the amount of drugs liberated over time during the in vitro release assay. The reversed-phase method allowed for the simultaneous determination of dexamethasone and melatonin, which were respectively detected at 240.5 and 222.7 nm. Chromatographic separation was performed using an Ascentis® C18 HPLC Column (25 cm × 4.6 mm, 5 µm) with an isocratic mobile phase composed of methanol-water (70:30, v/v) with 1.0 mL min−1 flow rate. The two procedures were validated analytically in terms of system suitability testing, specificity, linearity, precision, accuracy, sensitivity, and robustness. Both the validated procedures were applied to characterize DX-MEL-MSs and were found appropriate to quantify the drug quantities encapsulated and estimate their release profile over 10 days. The validation study designed in this work can be helpful for planning any other protocols that refer to the quantification of PLGA based drug delivery systems.

Methotrexate-loaded polymeric lipid hybrid nanoparticles (PLHNPs): a reliable drug delivery system for the treatment of glioblastoma

Polymeric lipid hybrid nanoparticles (PHLNPs) are core-shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) and glyceryl tripalmitate prepared using solvent injection and homogenisation method for a glioblastoma treatment option. The MTX-loaded PLHNPs optimised by Box–Behnken design to minimise particle size, higher entrapment efficacy and maximise MTX concentration in the brain at 4 h. The particle size, entrapment efficacy, concentration of drug in the brain at 4 h, zeta potential, and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51–233.37 nm, 70.56–86.34%, 6.38–12.38 μg/mL, 25.78–36.31 mV and 1.02–5.32. In-vitro drug release studies, cellular internalisation of optimised formulation against U-87 MG shows good anticancer effects.

Fabrication and development of controlled release PLGA microneedles for macromolecular delivery using FITC-Dextran as model molecule

The use of biodegradable polymers has been prominent in the field of drug delivery due to its degradability and biocompatible properties. These polymers when used to prepare microneedles, impart high mechanical strength, sustained drug release profile, and long term biocompatibility. In this study, PLGA (poly (D, L-lactic co-glycolic acid)) and PVA (Polyvinyl Alcohol) were used in combination to optimize the microneedle fabrication for high molecular weight FITC Dextran (4 kDa MW) to be used as a model drug. FITC-Dextran loaded PLGA microneedles were fabricated using a mold casting technique. MNs were characterized for the textural properties, FITC-Dextran release profile, and in-vitro permeation profile. The fate of microneedles in the skin (ex vivo) was characterized using fluorescence and confocal imaging. The FITC -Dextran MNs (10 × 10 array) had a dimension of 415 ± 2.65 μm height, 207 ± 1.63 μm width of the base and a needle pitch of 463 ± 1.45 μm. The texture analysis data showed puncture force for FITC-Dextran loaded PLGA microneedles (28.46 ± 0.23 g) and PLGA microneedles (16.92 ± 0.04 g). The Cumulative permeation of FITC-Dextran after 48 h was 2.34 ± 0.40 μg/cm2 and it showed a 31 fold higher permeation profile than its respective control. Ex vivo imaging studies were used to characterize the fluorescence intensity of FITC-Dextran in the skin. This study demonstrates that incorporating higher molecular weight molecules into PLGA microneedles proved to be an effective strategy to sustain the release of macromolecules across stratum corneum/epidermis for transdermal delivery.

Polymer-based prolonged-release nanoformulation of duloxetine: fabrication, characterization and neuropharmacological assessments

Objective The poly D, L–Lactic-co-glycolic acid (PLGA) and Polycaprolactone (PCL) have been widely applied for developing the prolonged-release formulation. The current study explores the application of these polymers for developing prolonged-release nanosphere of Duloxetine (DLX). Developing a prolonged release parenteral nanosphere formulation of DLX would be overcoming pitfalls like acid-labile degradation, first-pass metabolism and erratic bioavailability along with long-term therapeutic benefit in the treatment of depression. Methods DLX-loaded PLGA and PCL nanospheres were prepared by using the emulsion solvent evaporation technique. The developed formulation was compared with DLX oral solution concerning brain estimation. The prepared nanospheres were subjected to the morphology of the drug particles, polydispersity Index (PDI), distribution size, zeta potential, entrapment efficiency and percentage yield to generate a proof of concept. Results DLX-loaded polymeric nanosphere exhibited the uniform size from 89.48 nm to 100.9 nm. The entrapment efficiency was in the range of 74.93 to 77.49, respectively, of PLGA and PCL formulation. The FSEM image affirmed smooth spherical morphology. A good PDI and negative zeta potential value (−31.3 mV for F1 and −30.7 mV for F2) supported the stability of the nanosphere. The brain concentration of the drug was three times enhanced supporting the effectiveness of the nanosphere during pharmacodynamic and pharmacokinetic studies. Conclusion The intramuscular DLX-loaded nanospheres signify improved brain availability relative to DLX solution. This can be a blueprint for the effective and targeted brain delivery of CNS drugs.

Combination of carotenoids from Spirulina and PLA/PLGA or PHB: New options to obtain bioactive nanoparticles

The use of poly-β-hydroxybutyrate (PHB) is an alternative polymer that can be considered environment friendly and renewable to prepare nanoparticles of carotenoids. This study aimed to develop and characterize aqueous dispersion nanoparticles and lyophilized nanoparticles of carotenoid extract obtained from Spirulina sp. LEB 18 by nanoprecipitation, using poly d,l-lactic acid (PLA)/poly d,l-lactic-co-glycolic acid (PLGA) (75:25 w/w) or PHB as encapsulants. The samples were characterized for the particle size, polydispersity index, zeta potential, apparent viscosity, pH, color parameters, ultraviolet–visible (UV/Vis) spectrophotometry, carotenoid profile, encapsulation efficiency, morphology, and thermal analysis. Nanoparticles containing microalgae carotenoid extract showed average particle diameter on a nanoscale (<200 nm), high homogeneity and stability, high thermal stability, and encapsulation efficiency carotenoid (>80%) when compared to nanoparticles containing β-carotene synthetic. PHB or PLA/PLGA as encapsulating material in the production of nanoparticles from microalgae carotenoids can be a polymeric alternative capable of promoting greater stability and application of carotenoids.

Preparation, evaluation, and in vitro cytotoxicity studies of artesunate-loaded glycyrrhetinic acid decorated PEG-PLGA nanoparticles

Objective The objective of this study was to prepare the liver targeting drug delivery system (TDDS) of artesunate (ART)-loaded polyethylene glycol (PEG)-poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) modified by glycyrrhetinic acid (GA), and evaluate its in vitro cytotoxicity. Significance The GA-PEG-PLGA-ART NPs enhanced the in vitro cytotoxicity on HCC cell lines. The development of GA-PEG-PLGA NPs will greatly push the clinical applications of ART as a novel anticancer drug. Methods The NPs were prepared using solvent evaporation method, and the formulation was optimized through an orthogonal design. In addition, physical properties were determined, including particle size, polydispersity index (PDI), zeta potential (ZP), morphology, drug loading capacity (LC) and encapsulation efficiency (EE), and in vitro drug release. Moreover, the in vitro cytotoxicity of NPs with three human cancer cell lines viz. HepG2, Hep3B, and SMCC-7721 was conducted using the SRB assay. Additionally, lyophilization was conducted to improve the long-term physical stability. Results The GA-PEG-PLGA-ART NPs have spherical shape, small particle size (around 88 nm) with a narrow size distribution (PDI < 0.3), high drug LC (up to 59.3 ± 1.65%), and high EE (up to 73.13 ± 5.17%). In vitro drug release behavior showed that drugs were released from NPs in a sustained and controlled release pattern. Cytotoxicity study indicated the NPs achieved lower cancer cell survival fraction. The GA-PEG-PLGA NPs freeze-dried with 3% (w/v) of mannitol showed better effect on long-term physical stability. Conclusion The GA-PEG-PLGA-ART NPs appear as a potential liver targeted intracellular delivery platform for ART.

Duodenal Histomorphological Changes in Broilers Administered poly d, l-lactic-coglycolic acid (PLGA ) Nanoparticles Encapsulated with Peptide

This research was carried out to evaluate the effect of poly d, l-lactic-coglycolic acid(PLGA) nanoparticles loaded with peptide (as vaccine) on histomorphological in duodenum of broiler chick. A total of ninety eight, one day old ,unsexed broiler( Rose) chicks were divided randomly into seven groups( 2 replicate in each group) as follows:G1-control,G2 - chicks received traditional vaccine of infectious bursal disease(Volvac@ IBD MLV) ,G3 – Chicks Received PLGA nanoparticles only, G4,G5,G6 and G7 – chicks were received prepared vaccine at 160, 80, 40,and 20 μg of peptide loaded PLGA respectively. At the end of the experiment histopathological examination of duodenum section and histomorphological changes were examined. The histopathological examination of duodenal sections shows an elongation and infiltration of lamina propria (LP) with increase villi height and crypt depth in groups that received PLGA alone and those received peptide loaded PLGA. At the same time these groups reveal an increase in mucosal thickness and in length and width of villi. The histomorphological examination in this study show thicker mucosal layer with deeper crypt in duodenum of broilers that subjected to PLGA administration alone or to different concentration of peptide loaded PLGA compared to G1 and G2. These findings are accompanied by a high density of goblet cells and lower villus hight/crypt depth (V/CD) ratio. All groups show mononuclear cells (MNCs) infiltration in submucosa ofduodenum. In-conclusion, the administration of PLGA nanoparticles is strongly linked to the improvement of the physiological and immunological features of the birds.

Lipid Vesicles Loaded with an HIV-1 Fusion Inhibitor Peptide as a Potential Microbicide.

The effective use of fusion inhibitor peptides against cervical and colorectal infections requires the development of sustained release formulations. In this work we comparatively study two different formulations based on polymeric nanoparticles and lipid vesicles to propose a suitable delivery nanosystem for releasing an HIV-1 fusion inhibitor peptide in vaginal mucosa. Polymeric nanoparticles of poly-d,l-lactic-co-glycolic acid (PLGA) and lipid large unilamellar vesicles loaded with the inhibitor peptide were prepared. Both formulations showed average sizes and polydispersity index values corresponding to monodisperse systems appropriate for vaginal permeation. High entrapment efficiency of the inhibitor peptide was achieved in lipid vesicles, which was probably due to the peptide’s hydrophobic nature. In addition, both nanocarriers remained stable after two weeks stored at 4 °C. While PLGA nanoparticles (NPs) did not show any delay in peptide release, lipid vesicles demonstrated favorably prolonged release of the peptide. Lipid vesicles were shown to improve the retention of the peptide on ex vivo vaginal tissue in a concentration sufficient to exert its pharmacological effect. Thus, the small size of lipid vesicles, their lipid-based composition as well as their ability to enhance peptide penetration on vaginal tissue led us to consider this formulation as a better nanosystem than polymeric nanoparticles for the sustained delivery of the HIV-1 fusion inhibitor peptide in vaginal tissues.

Formulation and in vitro characterization of long-acting PLGA injectable microspheres encapsulating a peptide analog of LHRH

The present study aimed to formulate triptorelin acetate (TA) into poly (D, L-lactic-co-glycolic) acid (PLGA) based injectable sustained-release microspheres (TA-PLGA-MS) by usingdouble emulsion solvent extraction/evaporation (DESE) technique and investigate the effects of various material attributes and process parameters on the quality attributes such as size, shape, surface morphology, encapsulation efficiency (EE) and in vitro release behavior of these microspheres. Variable compositions of the outer water phase, type of the organic solvents, volume ratios of inner water phase to oil phase, PLGA concentrations, and the powers for emulsification in the preparation of the microspheres showed an influence on their quality attributes. An optimal formulation (F-2) obtained from this univariate approach possess an excellent EE value of 63.5% ± 3.4% and an average volumetric particle size of 35.3 ± 1.8 μm. This formulation was further accomplished with different solidification rates assisted by variable incubation temperatures, which exhibited an impact on the shape/surface and inner morphology of the microspheres. The resultant microspheres also displayed different in vitro release patterns. The matrices processed with a high incubation temperature conferred the fastest and the most complete drug release profile over the period of 63 days. Thus, the solidification rate could be identified as one of the critical process parameters that affected the quality of the PLGA based injectable microspheres specifically designed for the prolonged delivery of TA.

Comparative Study of PLGA in-situ Implant and Nanoparticle Formulations of Entecavir; in-vitro and in-vivo evaluation

Entecavir (Baraclude®) is used daily as a long-term treatment for hepatitis-B virus infections. In this study a sustained injectable biodegradable in-situ implant (ISI) and polymeric nanoparticles (NPs) of Entecavir were prepared using Poly-d,l-lactic-co-glycolic acid (PLGA) polymer and evaluated for their shape, saturation solubility, in-vitro release and in-vivo efficacy. The pharmacokinetic parameters of Entecavir formulations were studied in rats following intramuscular injection, and the data was analyzed using one-way analysis of variance (ANOVA). TEM photographs showed that the ISI had a porous surface after exposure to Sörensen phosphate buffer pH 7.4 for 24 h, and Entecavir loaded NPs had a spherical structure with a smooth surface. The entrapment efficiency of Entecavir NPs was in the range of 47.03–77.84%. The pharmacokinetic studies showed a significant reduction (p < 0.05) in the Cmax from 353.75 for the pure Entecavir to 16.70 and 172.85 ng/ml for the NPs and ISI formulations, respectively. The AUC0-∞ also increased significantly from 211.32 ng/ml.h for pure Entecavir to 1520.64 and 2363.52 ng/ml.h for ISI and NP formulations, respectively. This study showed the feasibility of intramuscular ISI and NP formulations loaded with Entecavir which exhibit sustained release profiles and a promising strategy for the treatment of chronic hepatitis-B.

Exenatide-loaded inside-porous poly(lactic-co-glycolic acid) microspheres as a long-acting drug delivery system with improved release characteristics

The glucagon-like peptide-1 receptor agonist exenatide (EXT) is an effective treatment for type 2 diabetes. However, this peptide has a short biological half-life and the delayed release characteristic of current formulations limit its clinical application. Herein, we prepared EXT-loaded inside-porous poly(d,l-lactic-co-glycolic acid (PLGA) microspheres with outside layers (EXT-PMS) using a W1/O/W2 emulsion method with a microfluidic technique and its fabrication and formulation conditions were systematically investigated. In vitro dissolution experiments showed that the PLGA concentration, proportion of drug and oil phase, and the number and size of pores strongly affected the release behaviors of EXT-PMS. In vitro, the optimized EXT-PMS with large internal pores exhibited rapid and stable release without a lag phase. In a rat model, subcutaneous administration of the product yielded plasma concentrations of EXT that was sustained for 30 days with low burst and no delayed-release effect. The preparation of inside-porous microspheres is lighting up the development of long-acting drug delivery systems for other drugs with favorable release characteristics.