Drug in adhesive transdermal patch containing antibiotic-loaded solid lipid nanoparticles.

The structure of the skin only allows those hydrophobic elements to penetrate through the depth of the skin with low molecular weight (less than 500 Da) and low daily dose (less than 100 mg/day). Skin penetration of many drugs such as antibiotics at a high daily dose remains an unresolved challenge. In this study a transdermal patch using cephalexin as an antibiotic drug model was developed. Cephalexin was loaded into α-tocopherol succinate-based solid lipid nanoparticles (SLNs). Cephalexin-loaded SLNs with a drug/lipid ratio of 20%, diameter of 180 ± 7 nm, and drug loading 7.9% led to the greatest inhibition zone of Staphylococcus aureus and showed the highest skin permeation capabilities. Cephalexin-loaded SLNs were distributed into poly-iso-butylene adhesive solution and final patches prepared using solvent casting. The physico-chemical characteristics, in vitro drug release, antimicrobial efficacy, and skin cell proliferation properties of patches were evaluated. Results indicated that the optimal transdermal patch formulation containing 90% adhesive solution, 7% cephalexin, and 3% cephalexin-loaded SLNs (with antibiotic content approximately 28% less) inhibited growth of S.aureus better than the formulation containing 90% adhesive solution and 10% cephalexin. In vitro evaluation of the growth of human fibroblast skin cells in media with the optimal patch exhibited greater proliferation (about 25.5%) than those in media without the patch.

Fast-dissolving oral films containing dextromethorphan/phenylephrine for sinusitis treatment: formulation, characterization and optimization.

This work uses optimization study to formulate a patient-friendly antitussive fast-dissolving oral film based on phenylephrine hydrochloride (Phen) and dextromethorphan hydrobromide (Dex). The designed films were based on hydroxypropylmethyl cellulose (HPMC) with two grades (E5 and E50) as a film-forming polymer by the solvent-casting method. Polyethylene glycol with two molar masses (400 and 1000) was used as a plasticizer, while aspartame was used as a sweetener and microcrystalline cellulose intended to act as a disintegrant. To find an optimum formulation, a response surface methodology and a central composite design were employed. The percentage of HPMC E50, and PEG, as a plasticizer, were considered to be the design factors. Film thickness, surface pH, disintegration time, dissolution percent, tensile strength, elongation percent and folding endurance were considered to be the responses. A film with 11.46% E50, 88.54% E5, 25% of two drugs (8.4% of Phen and 16.6% of Dex) and 18.54% plasticizer is designed and prepared as the optimum formulation for Phen/Dex fast-dissolving oral films, with 95% confidence levels.

Injectable chitosan hydrogel embedding modified halloysite nanotubes for bone tissue engineering.

Low mechanical strength and untargeted osteoinduction of chitosan hydrogel limit its application for bone regeneration. This study aimed to develop an injectable chitosan hydrogel with enhanced mechanical strength and improved osteoinductivity for bone tissue engineering. For this purpose, chitosan-modified halloysite nanotubes (mHNTs) were synthesized first. Then, icariin as a bone inducer was loaded into mHNTs (IC@mHNTs), resulting in a sustained drug release system. Further, nanocomposite chitosan/mHNTs hydrogels were prepared by the sol-gel transition, leading to decreased gelation time and temperature and enhanced mechanical strength of the resulting scaffolds. The mesenchymal stem cells were encapsulated into the hydrogels, and in vitro viability assays showed scaffold biocompatibility. Moreover, embedded mHNTs or IC@mHNTs in the scaffold resulted in enhanced proliferation and bone differentiation of encapsulated cells. It was collectively demonstrated that the injectable in situ forming nanocomposite chitosan hydrogel loaded with IC@mHNTs is a promising candidate for bone regeneration.

Electrospun PCL scaffold modified with chitosan nanoparticles for enhanced bone regeneration.

The encapsulation of ascorbic acid within chitosan nanoparticles (CHNs), embedded in a fibrous structure of a dexamethasone (Dex)-loaded PCL scaffold, provides a new plan for osteogenic differentiation of mesenchymal stem cells. This electrospun PCL fibrous scaffold can release Dex, as bone differentiation initiator, and ascorbic acid, as bone differentiation enhancer, in an approximately sustained release pattern for about 2 weeks. Ascorbic acid-loaded CHNs were prepared by electrospraying a mixture of chitosan and ascorbic acid, and Dex-containing PCL fibers were prepared by electrospinning a mixture of PCL and Dex. The final PCL/chitosan bilayer scaffolds were obtained by the sequential employment of electrospinning and electrospraying methods. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) confirmed that the CHNs were successfully incorporated into the fibrous PCL matrix. The improved proliferation of hMSCs cultured on the PCL/chitosan scaffolds was also verified. Osteogenic assays showed an increase in alkaline phosphatase activity and mineral deposits. The expression of bone-specific genes also confirmed the osteogenic differentiation of cells cultured on these PCL/chitosan bilayer scaffolds. Dual-drug-loaded PCL/chitosan scaffold enhanced the osteoblast differentiation of hMSC cells and can be served as a potential scaffold for bone tissue engineering.

Preparation, optimization, and evaluation of midazolam nanosuspension: enhanced bioavailability for buccal administration.

Midazolam is considered as one of the best first-line drugs in managing status epilepticus in children who require emergency drug treatment. Due to poor water solubility, oral bioavailability of midazolam is relatively low. To improve its dissolution and absorption, midazolam nano-suspensions were formulated with different stabilizers using the ultrasonic technique. A combination of Tween 80 and Poloxamer (TP) was considered as one stabilizer and 3-methyl chitosan (TMC) as another stabilizer. The ratio of the stabilizers was selected as an independent variable, and their effects on the particle size and the zeta potential were evaluated by the simplex lattice mixture method. The freeze-dried optimized midazolam nano-suspension powder was characterized by particle-size analysis, SEM, the stability test, and the dissolution test. The optimized midazolam nano-suspension (containing 76% TMC and 24% TP) had a mean particle size of 197 ± 7 nm and a zeta potential of 31 ± 4 (mV). The stability test showed that the midazolam nano-suspension is stable for 12 months. In the in vitro dissolution test, the midazolam nano-suspension showed a marked increase in the drug dissolution percentage versus coarse midazolam. In the in vivo evaluation, the midazolam nano-suspension exhibited a significant increase in the Cmax and the AUC0-5, and a major decrease in Tmax. The overall results indicate the nano-suspension of midazolam is a promising candidate for managing status epilepticus in children in emergency situation.

Development and Evaluation of an Anti-Epileptic Oral Fast-Dissolving Film with Enhanced Dissolution and In vivo Permeation.

OBJECTIVES: The main objective of this novel study was to develop midazolam hydrochloride fast dissolving oral films (FDFs) using solvent casting method and to evaluate the characteristics of the optimum formulation through in vitro and in vivo analysis. The FDFs are new favorable solid dosage forms that deliver drugs rapidly to the blood circulation system and have great advantages in the emergent control of severe neuropathic attacks in children. METHODS: Midazolam nanosuspensions were prepared using the ultrasonic method and then incorporated in the hydroxypropyl methyl cellulose (HPMC)/pullulan polymeric matrix with other excipients like glycerol and cellulose nanofiber as a softener and a compatibilizer, respectively. The prepared films were evaluated for mechanical properties, morphology study, disintegration time, and dissolution time. RESULTS: SEM images of FDFs showed the uniform distribution of spherical nanoparticles in the polymeric matrix. A film with 36% HPMC, 64% pullulan, and 21% glycerin was selected as the optimum formulation by the Design Expert 7 software. The optimum film was stable for three months. CONCLUSION: The pharmacokinetic parameters of midazolam oral film in comparison to coarse midazolam suspension exhibited significant increase in AUC, Cmax, and a good decrease in Tmax. The overall results showed the enhanced in vivo orotransmucosal absorption of poorly water-soluble drugs via the insertion of drugs nanosuspension in buccal films.

Formulation, Characterization, and Optimization of Captopril Fast-Dissolving Oral Films.

This work aimed to using optimization study to formulate a patient-friendly captopril fast-dissolving oral film with satisfactory disintegration time. Films were made with pullulan and hydroxypropyl methyl cellulose (HPMC) by using the solvent-casting method. Cellulose nanofiber (CNF) was used as a compatibilizer and glycerine was used as a plasticizer. In order to find an optimum formulation, a response surface methodology and a central composite design were employed. The concentration percentages of pullulan and glycerine were considered to be the design factors. Disintegration time, tensile strength, percent elongation at break, and folding endurance were considered to be the responses. The results showed that CNF improved the compatibility and tensile strength of the pullulan and HPMC blend. Also, the rigid nature of CNF reduced the film elongation but the addition of glycerine improved its flexibility. All formulations showed an acceptable uniformity content and dissolution rate. Complete dissolution for all formulations occurred within 2 min. Films with 26% pullulan, 74% HPMC, 1% CNF, and 5% glycerine were reported to be optimum formulations for captopril fast-dissolving oral films, with 95% confidence levels. The in vivo comparison of optimized formulation with a conventional captopril sublingual tablet exhibited significant increase in AUC (~ 62%) and Cmax (~ 52%) and a major decrease in Tmax (~ 33%). The overall results showed that the captopril FDF is a promising candidate for enhanced in vivo orotransmucosal absorption.

Preparation and optimization of rivastigmine-loaded tocopherol succinate-based solid lipid nanoparticles.

Rivastigmine hydrogen tartrate (RHT) is a pseudo-irreversible inhibitor of cholinesterase and is used for the treatment of Alzheimer's. However, RHT delivery to the brain is limited by the blood-brain barrier (BBB). The purpose of this study was to improve the brain-targeting delivery of RHT by producing and optimizing rivastigmine hydrogen tartrate-loaded tocopherol succinate-based solid lipid nanoparticles (RHT-SLNs). RHT-SLNs were prepared using the microemulsion technique. The impact of significant variables, such as surfactant concentration and drug/lipid ratio, on the size of RHT-SLNs and their drug loading and encapsulation efficiency was analysed using a five-level central composite design (CCD). The minimum size of particles and the maximum efficiency of loading and encapsulation were defined according to models derived from a statistical analysis performed under optimal predicted conditions. The experimental results of optimized RHT-SLNs showed an appropriate particle size of 15.6 nm, 72.4% drug encapsulation efficiency and 6.8% loading efficiency, which revealed a good correlation between the experimental and predicted values. Furthermore, in vitro release studies showed a sustained release of RHT from RHT-SLNs.

Fluorescein isothiocyanate-dyed mesoporous silica nanoparticles for tracking antioxidant delivery.

This study investigated the cellular uptake of fluorescein isothiocyanate-labelled mesoporous silica nanoparticles (FITC-MSNs), amine-functionalised FITC-MSNs (AP-FITC-MSNs) and their gallic acid (GA)-loaded counterparts. Mesoporous silica nanoparticles were labelled with fluorescein isothiocyanate, functionalised by 3-aminopropyltriethoxysilane (APTES) (AP-FITC-MSNs) and then loaded by GA. All nanoparticles were characterised by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and X-ray diffraction. The cytotoxicity of different concentrations of dyed nanoparticles was investigated using (3-(4,5-trihydroxybenzoic acid, dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry. TEM images showed that the average particle sizes of FITC-MSNs and AP-FITC-MSNs were about 100 and 110 nm, respectively. These nanoparticles were internalised by Caco-2 cells, accumulated and dispersed into the cytoplasm, nucleus, and subcellular organelles. Nanoparticles containing GA clearly decreased the viability of cells. FITC-MSNs showed no toxicity on Caco-2 cells at concentrations of ≤50 µg/ml. Functionalisation of FITC-MSNs using APTES decreased toxicity effects on the cells. It was found that FITC-MSNs can be applied at low concentrations as a marker in the cells. In addition, AP-FITC-MSNs showed better biocompatibility with Caco-2 cells than FITC-MSNs, because of their positive surface charges.

Mesoporous silica nanoparticles for efficient rivastigmine hydrogen tartrate delivery into SY5Y cells.

Rivastigmine hydrogen tartrate (RT) is a molecule with both hydrophilic and hydrophobic properties used for the treatment of the Alzheimer's disease. In this work, the larger pore size of mesoporous silica nanoparticles (P1-MSN) was synthesized and then, P1-MSN were functionalized by succinic anhydride (S-P1-MSN) and 3-aminopropyltriethoxysilane (APTES) (AP-CO-P1-MSN) using the grafting and co-condensation methods, respectively. A new method was used for the functionalization of P1-MSN by succinic anhydride at room temperature. Nanoparticles were characterized by special instrumental analysis and loaded by RT. Maximum entrapment efficiency and RT loading percentage into P1-MSN, AP-CO-P1-MSN and S-P1-MSN were respectively obtained as 21.26 and 25.5%, 41.5 and 49.8%, and 11.9 and 14.28% for 24 h. In the simulated gastric and body fluids, the release rate of RT-loaded AP-CO-P1-MSN (AP-CO-P1-MSN-RT) was lower than that of other RT-loaded nanoparticles. In oral pathway, the sustained release of RT was observed in AP-CO-P1-MSN-RT. Moreover, no cytotoxicity effect was observed for P1-MSN, but the cells treated by AP-CO-P1-MSN showed a reduction in SY5Y cell viability due to easy entrance of these nanoparticles and their accumulation in different parts of the cell as observed by TEM.

Skeletal muscle regeneration via engineered tissue culture over electrospun nanofibrous chitosan/PVA scaffold.

Skeletal muscle tissue shows a remarkable potential in regeneration of injured tissue. However, in some of chronic and volumetric muscle damages, the native tissue is incapable to repair and remodeling the trauma. In the same condition, stem-cell therapy increased regeneration in situations of deficient muscle repair, but the major problem seems to be the lack of ability to attachment and survive of injected cells on the exact location. In this study, chitosan/poly(vinyl alcohol) nanofibrous scaffold was studied to promote cell attachment and provide mechanical support during regeneration. Scaffold was characterized using scanning electron microscope, X-ray diffraction, and tensile test. Degradation and swelling behavior of scaffold were studied for 20 days. The cell-scaffold interaction was characterized by MTT assay for 10 days and in vivo biocompatibility of scaffold in a rabbit model was evaluated. Results showed that cells had a good viability, adhesion, growth, and spread on the scaffold, which make this mat a desirable engineered muscular graft. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1720-1727, 2016.

In vitro osteogenic induction of human marrow-derived mesenchymal stem cells by PCL fibrous scaffolds containing dexamethazone-loaded chitosan microspheres.

This research reports the encapsulation of dexamethasone (Dex) within the chitosan microspheres (CSMs) embedded in a fibrous structure of poly(ɛ-caprolactone) (PCL) to provide a platform for osteogenic differentiation of human mesenchymal stem cells (hMSCs). Dex loaded CSMs were prepared by spray drying a mixture of chitosan and Dex. Then, they were electrospun with PCL solution to create a bilayer fibrous scaffold (PCL/CSMs-Dex). The CSMs act as good depots for sustained release of Dex over a period of 14 days, without noticeable burst release. This is mainly attributed to the core-shell structure of the final PCL/CSMs-Dex-matrix, which could prolong the release and eliminate the initial burst. The water contact angle of PCL scaffolds decreased from 141.4 ± 3.8 to 118.4 ± 7.6 in the presence of CSMs. Improved proliferation of hMSCs cultured on PCL/CSMs-Dex scaffolds was also evidenced. Furthermore, osteogenic assays showed an increase in alkaline phosphatase activity and mineral deposits. The expression of bone-specific genes also confirmed the osteogenic differentiation of cells cultured on these Dex-loaded core-shell structures. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1657-1667, 2016.

Preparation and Characterization of Rivastigmine Transdermal Patch Based on Chitosan Microparticles.

Here we report a novel approach for preparation of a 6-day transdermal drug delivery system (TDDS) as treatment for mild to moderate Alzheimer's disease. The spray drying method was used to prepare microparticles containing the anti-Alzheimer drug, Rivastigmine, in combination with the natural polymer, chitosan, for transdermal drug delivery applications. The content of the drug was determined by High Performance Liquid Chromatography (HPLC) method which was validated as per FDA guidelines. The morphology and size range of the microparticles were determined; and the effect of drug concentration in the solution injected into the spray dryer on the particles characterizations was studied. The stability of Rivastigmine at high temperature was confirmed using FTIR analysis as well as a validate HPLC assay. The obtained results show that the drug was stable at high temperatures with 7 to 42% loading in the microparticles, and the higher drug concentrations of the solution injected into the spray dryer resulted in increase of the drug loading, surface drug and microparticles distortion. The TDDS containing the microparticles was also prepared with microparticle to dry adhesive ratios of 5, 10 and 15% using acrylic adhesive. Based on adhesion properties of the patches, gained from the probe tack and the peel adhesion 180° tests, and the 15% patch by having more drug content per unit area of the patch, and still having similar adhesion properties was compared to the microparticles-free patch of 5.1% Rivastigmine salt (equivalent to the drug content of the 15% patch) from the permeation point of view by using Franz cell diffusion over 6 days. The drug permeation rate from the microparticle-free patch was slower than the 15% microparticles patch, which is the result of crystallization of Rivastigmine salt in the acrylic adhesive. The 6-day-prepared TDDS can be considered as an alternative for one-week application of 6 Exelon patches.

Survival, proliferation and differentiation enhancement of neural stem cells cultured in three-dimensional polyethylene glycol-RGD hydrogel with tenascin.

Polyethylene glycol hydrogel (PEG) conjugated with arginyl glycyl aspartic acid (RGD) (PEG-RGD) has been considered to be a scaffold in three-dimensional (3D) culture that improves neurite outgrowth; on the other hand, tenascin C controls neural growth and differentiation. In this study, the effect of a combined RGD and tenascin C mixture in 3D culture (3D-PEG-RGD-TnC) on the survival, growth and differentiation of neural stem cells. The viability of the culture has been evaluated by live/dead assay and the results show that the viability of NSCs in 3D-PEG-RGD-TnC is significantly higher than its value in 3D-PEG-RGD. The proliferation was evaluated by MTS test and was found to be slightly improved but statistically not significant. Accordingly, the differentiation was evaluated by immunoreactivity to nestin, neurofilament 68, neurofilament 160, neurofilament 200 and GFAP; and the expression of nestin, neuro D, musashi1, ß-tubulin III, GFAP, MBP and Oct4 was studied using RT-PCR. The results showed enhancement of the differentiation of NSCs into the neuronal phenotype in 3D-PEG-RGD-TnC. The morphology of NSCs cultured in 3D-PEG-RGD-TnC showed neurite outgrowths and increase in the contact between the differentiated cells' extensions. The conclusion of this study was that NSC survival, proliferation and differentiation are enhanced when the cells are cultured in 3D-PEG-RGD-TnC.

Thermosensitive hydrogel for periodontal application: in vitro drug release, antibacterial activity and toxicity evaluation.

Injectable thermosensitive chitosan hydrogel is an attractive temperature-induced sol-gel solution that is widely used in drug delivery and biomedical applications. In this study, an injectable antimicrobial delivery system for periodontal treatment based on chitosan/gelatin/ß-glycerolphosphate solution has been developed. The result of thermal and mechanical evaluations of chitosan/gelatin/ß-glycerolphosphate hydrogel showed that adding gelatin to chitosan/ß-glycerolphosphate solution significantly decreased gelling time and increased gel strength at 37℃. The antimicrobial agents chosen for release studies were metronidazole with a low molecular weight and vancomycin hydrochloride with a high molecular weight. The initial burst and total in vitro drug release for metronidazole was 13% and 67%, respectively. The initial burst and total drug release for vancomycin hydrochloride was relatively low at 3% and 23%, respectively. The momentary and total percentage of metronidazole accumulated in the phosphate buffer revealed that chitosan/gelatin/ß-glycerolphosphate can develop and maintain sustained release of metronidazole in concentrations that are effective for eliminating pathogenic bacteria over time. Cytotoxicity evaluations show that chitosan/gelatin/ß-glycerolphosphate thermosensitive hydrogel is a drug carrier with no cytotoxic effects.

In vitro and in vivo evaluation of thermosensitive chitosan hydrogel for sustained release of insulin.

Injectable In situ gel-forming chitosan/ß-glycerol phosphate (CS/ß-Gp) solution can be introduced into the body in a minimally invasive manner prior to solidifying within the target tissue. This hydrogel is a good candidate for achieving a prolonged drug delivery system for insulin considering its high molecular weight. In addition to the physicochemical characterization of this hydrogel, in vitro and in vivo applications were studied as a sustained insulin delivery system. In the in vitro release studies, 19-63% of total insulin was released from the CS/ß-Gp hydrogel within 150 h at different ß-Gp and insulin concentrations. The best formulation was selected for in vivo experimentation to control the plasma glucose of diabetic mice models. The hypoglycemic effect of this formulation following subcutaneous injection in diabetic mice lasted 5 d, significantly longer than that of free insulin solution which lasted several hours.

Drug release from enzyme-mediated in situ-forming hydrogel based on gum tragacanth-tyramine conjugate.

In the present study, injectable hydrogels based on gum tragacanth-tyramine conjugate were prepared by enzymatic oxidation of tyramine radicals in the presence of hydrogen peroxide. Then, in vitro release of bovine serum albumin and insulin as model protein drugs from this polymeric network was investigated. Also, to improve the properties of this hydrogel, a blended hydrogel composed of tyramine-conjugated gelatin and tyramine-conjugated tragacanth was prepared. Experimental results showed that the gelation time ranged from 3 to 28 s depending on the polymer and enzyme concentrations. Results of morphological investigation of hydrogels indicated that the average pore size of hydrogels varied from 120 to 160 µm. Swelling degree of hydrogels and the rate of drug release decreased by increasing of hydrogen peroxide and polymer concentrations. The release profile of drug from hydrogels followed Higuchi and Fickian diffusion mechanism. Finally, it was shown that the swelling characteristics and drug release behavior of this polymeric network could be improved by blending it with tyramine-conjugated gelatin.

Injectable thermosensitive chitosan/glycerophosphate-based hydrogels for tissue engineering and drug delivery applications: a review.

Recently, great attention has been paid to in situ gel-forming chitosan/glycerophosphate (CS/Gp) formulation due to its high biocompatibility with incorporated cells and medical agents, biodegradability and sharp thermosensitive gelation. CS/Gp is in liquid state at room temperature and after minimally invasive administration into the desired tissue, it forms a solid-like gel as a response to temperature increase. The overview of various recently patented strategies on injectable delivery systems indicates the significance of this formulation in biomedical applications. This thermosensitive hydrogel has a great potential as scaffold material in tissue engineering, due to its good biocompatibility, minimal immune reaction, high antibacterial nature, good adhesion to cells and the ability to be molded in various geometries. Moreover, CS/Gp hydrogel has been utilized as a smart drug delivery system to increase patient compliance by maintaining the drug level in the therapeutic window for a long time while avoiding the need for frequent injections of the therapeutic agent. This review paper highlights the recent patents and investigations on different formulations of CS/Gp hydrogels as tissue engineering scaffolds and carriers for therapeutic agents. Additionally, the dominant mechanism of sol-gel transition in those systems as well as their physicochemical properties and biocompatibility are discussed in detail.

Preparation and investigation of sustained drug delivery systems using an injectable, thermosensitive, in situ forming hydrogel composed of PLGA-PEG-PLGA.

In situ gelling systems are very attractive for pharmaceutical applications due to their biodegradability and simple manufacturing processes. The synthesis and characterization of thermosensitive poly(D,L-lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymers as in situ gelling matrices were investigated in this study as a drug delivery system. Ring-opening polymerization using microwave irradiation was utilized as a novel technique, and the results were compared with those using a conventional method of polymerization. The phase transition temperature and the critical micelle concentration (CMC) of the copolymer solutions were determined by differential scanning calorimetry and spectrophotometry, respectively. The size of the micelles was determined with a light scattering method. In vitro drug release studies were carried out using naltrexone hydrochloride and vitamin B12 as model drugs. The rate and yield of the copolymerization process via microwave irradiation were higher than those of the conventional method. The copolymer structure and concentration played critical roles in controlling the sol-gel transition temperature, the CMC, and the size of the nanomicelles in the copolymer solutions. The rate of drug release could be modulated by the molecular weight of the drugs, the concentration of the copolymers, and their structures in the formulations. The amount of release versus time followed zero-order release kinetics for vitamin B12 over 25 days, in contrast to the Higuchi modeling for naltrexone hydrochloride over a period of 17 days. In conclusion, PLGA-PEG1500-PLGA with a lactide-to-glycolide ratio of 5:1 is an ideal system for the long-acting, controlled release of naltrexone hydrochloride and vitamin B12.

In vitro insulin release from thermosensitive chitosan hydrogel.

Recently, great attention has been paid to in situ gel-forming chitosan/glycerol-phosphate (chitosan/Gp) solution due to their good biodegradability and thermosensitivity. This in situ gel-forming system is injectable fluid that can be introduced into the body in a minimally invasive manner prior to solidifying within the desired tissue. At the present study, insulin release from chitosan/Gp solution has been investigated. Insulin in different concentrations was loaded in two formulations of chitosan/Gp solution and in vitro drug release was studied over a period of 3 weeks. Results indicated that the release of insulin from chitosan/Gp gel decreases by increasing in Gp salt and initial insulin concentration. Stability of released insulin was investigated by 8-anilino-1-naphthalenesulfonate probe. Results proved that insulin have been released in its native form. Because of simple preparation and administration, prolonged release of insulin and stability of released insulin, this in situ gel-forming system could be used as a controlled release delivery system for insulin.