Injectable thermosensitive PLGA-PEG-PLGA triblock copolymers-based hydrogels as carriers for interleukin-2

Thermosensitive PLGA-PEG-PLGA triblock copolymers with the DL-lactide/glycolide molar ratio ranging from 6/1 to 15/1 were synthesized by bulk copolymerization of DL-lactide, glycolide and PEG1500. The resulting copolymers are soluble in water to form a freely flowing fluid at room temperature but become hydrogels at body temperature. The release of IL-2 from the copolymer-based hydrogel in the phosphate buffer (pH 7.2) was studied at 37 degrees C under agitation. IL-2 was released from the copolymer-based hydrogels over 20 days in vitro and the release rate decreased with increasing copolymer concentration. The change of DL-lactide/glycolide molar ratio in the PLGA block of the copolymer had little effect on the IL-2 release. The released IL-2 remained 57-90% of its original activity during the release period. To evaluate the anti-tumor effect of the IL-2 loaded copolymer, solutions were injected subcutaneously to H22 tumor-bearing mice. IL-2 loaded copolymer hydrogel for in vivo use showed good anti-tumor effect. These results indicate that the thermosensitive PLGA-PEG-PLGA triblock copolymers could be a promising platform for sustained delivery of IL-2.     

Effect of bee venom peptide-copolymer interactions on thermosensitive hydrogel delivery systems

The objectives of this study were to investigate the potential interactions between the model protein drug (bee venom peptide, BVP) and thermosensitive poly(dl-lactide-co-glycolide-b-ethyleneglycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymers and to examine the drug-copolymer interactions on the in vitro drug release and hydrogel degradation. The PLGA-PEG-PLGA copolymers were synthesized by ring-opening copolymerization of dl-lactide and glycolide with PEG as an initiator. Drug-copolymer co-precipitate blends were prepared and analyzed by Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) to characterize the specific interactions between drug and copolymer. For the better understanding the drug-copolymer interactions on drug release, insulin was selected for comparison. The release of the two protein drugs from the copolymer-based hydrogels and hydrogel degradation was studied at 37 degrees C under agitation. The results of FTIR and XRD indicated that the hydrogen bonding interactions existed between the NH group of BVP and CO group of the copolymers. The insulin and BVP released from the copolymer hydrogel over 15 and 40 days, respectively. The BVP-copolymer interactions retarded the BVP release rate and degradation of hydrogel, but did not significantly affect the biological activity of BVP. These results indicate that the drug-copolymer interactions need to be considered when attempting to use PLGA-PEG-PLGA hydrogels as sustained delivery carriers of protein or peptide drugs.     

Injectable biodegradable temperature-responsive PLGA-PEG-PLGA copolymers: synthesis and effect of copolymer composition on the drug release from the copolymer-based hydrogels

Injectable biodegradable temperature-responsive poly(DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with DL-lactide/glycolide molar ratio ranging from 6/1 to 15/l were synthesized from monomers of DL-lactide, glycolide and polyethylene glycol and characterized by 1H NMR. The resulting copolymers are soluble in water to form free flowing fluid at room temperature but become hydrogels at body temperature. The hydrophobicity of the copolymer increased with the increasing of DL-lactide/glycolide molar ratio. In vitro dissolution studies with two different hydrophobic drugs (5-fluorouracil and indomethacin) were performed to study the effect of DL-lactide/glycolide molar ratio on drug release and to elucidate drug release mechanism. The release mechanism for hydrophilic 5-fluorouracil was diffusion-controlled, while hydrophobic indomethacin showed an biphasic profile comprising of an initial diffusion-controlled stage followed by the hydrogel erosion-dominated stage. The effect of DL-lactide/glycolide molar ratio on drug release seemed to be dependent on the drug release mechanism. It has less effect on the drug release during the diffusion-controlled stage, but significantly affected drug release during the hydrogel erosion-controlled stage. Compared with ReGel system, the synthesized copolymers showed a higher gelation temperature and longer period of drug release. The copolymers can solubilize the hydrophobic indomethacin and the solubility (13.7 mg/ml) was increased 3425-fold compared to that in water (4 microg/ml, 25 degrees C). Two methods of physical mixing method and solvent evaporation method were used for drug solubilization and the latter method showed higher solubilization efficiency.     

注射用蜂毒多肽温度敏感型缓释凝胶的制备及体外释放研究

目的制备注射用蜂毒多肽的温度敏感型缓释凝胶制剂并对其体外释药进行考察。方法以新型温度敏感聚丙交酯乙交酯聚乙二醇嵌段共聚物(PLGAPEGPLGA)为载体材料制备注射用蜂毒多肽缓释凝胶制剂,采用福林酚试剂法测定制剂在磷酸盐缓冲溶液中(pH7.4)的体外释放度,并对体外释放数据用KorsmeyerPeppas方程进行拟合。结果蜂毒多肽体外持续释放36d,其释药速率随聚合物的质量分数增加而降低,且聚合物分子结构中丙交酯比例增大对释药速率几乎没有影响。蜂毒多肽从凝胶中的释放初期以扩散为主,体外释放行为符合KorsmeyerPeppas方程,后期为凝胶溶蚀和药物扩散结合的作用机制。结论注射用蜂毒多肽的温度敏感型缓释凝胶制剂制备工艺简便,药物释放达到预期要求,同时说明温度敏感PLGAPEGPLGA嵌段共聚物作为注射用缓释给药系统的载体材料具有很好的应用前景。     

生物降解聚合物PLGA-PEG-PLGA的合成及表征

目的对生物降解聚合物PLGA-PEG-PLGA进行合成及表征。方法以丙交酯、乙交酯及PEG为原料,用开环聚合法合成生物降解聚合物PLGA-PEG-PLGA,并用DSC、GPC和1H-NMR对其结构进行表征。结果合成的聚合物为嵌段聚合物。由1H-NMR可知聚合物数均相对分子质量为6 400~8 000,重均相对分子质量为7 100~9 200。上述制备的聚合物的水溶液具有反向热敏性质。质量分数为30%的PLGA-PEG-PLGA(3)水溶液的胶凝(由溶胶变为凝胶)温度为33℃,符合人体生理温度。结论提供了一种新的生物降解性药物载体材料。     

Injectable block copolymer hydrogels for sustained release of a PEGylated drug

The paper employs the spontaneous physical gelling property of a biodegradable polymer in water to prepare an injectable sustained release carrier for a PEGylated drug. A series of thermogelling PLGA-PEG-PLGA triblock copolymers were synthesized. The PEGylated camptothecin (CPT) was also prepared and employed as the model of a PEGylated drug, and the solubility of this hydrophobic drug was significantly enhanced to over 150mg/mL. The model drug was completely entrapped into the polymeric hydrogel, and the sustained release lasted for 1 month. The mechanism of the sustained release was diffusion-controlled at the first stage and then was the combination of diffusion and degradation at the late stage. In vivo anti-tumor tests in mice further confirmed the efficacy of the model PEGylated drug released from the hydrogel. This work also revealed the specificity of the PEGylated drug in such a kind of carrier systems by decreasing the critical gelling temperature and increasing the viscosity of the sol. Due to the very convenient drug formulation and highly tunable release rate, an injectable carrier platform for PEGylated drugs is thus set up.     

In situ Hydrogels Prepared by Photo-initiated Crosslinking of Acrylated Polymers for Local Delivery of Antitumor Drugs

A triblock copolymer was synthesized by ring opening polymerization of ε‐caprolactone in the presence of poly(ethylene glycol) (PEG). The resulted PCL-PEG-PCL triblock copolymer, PEG and monomethoxy (MPEG) were functionalized by end group acrylation. NMR and FT-IR analyses evidenced the successful synthesis and functionalization of polymers. A series of photo-crosslinked hydrogels composed of acrylated PEG-PCL-Acr and MPEG-Acr or PEG-Acr were prepared by exposure to visible light using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as initiator. The hydrogels present a porous and interconnected structure as shown by SEM. The swelling performance of hydrogels is closely related to the crosslinking density and hydrophilic content. Addition of MPEG or PEG results in increase in water absorption capacity of hydrogels. In vitro degradation of hydrogels was realized in the presence of a lipase from porcine pancreas. Various degradation rates were obtained which mainly depend on the hydrogel composition. MTT assay confirmed the good biocompatibility of hydrogels. Importantly, in situ gelation was achieved by irradiation of a precursor solution injected in the abdomen of mice. Doxorubicin (DOX) was selected as a model antitumor drug to evaluate the potential of hydrogels in cancer therapy. Drug-loaded hydrogels were prepared by in situ encapsulation. In vitro drug release studies showed a sustained release during 28 days with small burst release. DOX-loaded hydrogels exhibit antitumor activity against A529 lung cancer cells comparable to free drug, suggesting that injectable in situ hydrogel with tunable properties could be most promising for local drug delivery in cancer therapy.     

Thermosensitive hydrogels of poly(methyl vinyl ether-co-maleic anhydride) – Pluronic® F127 copolymers for controlled protein release

Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez^® AN, GZ) and Pluronic^® F127 (PF127) copolymers (GZ–PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol–gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histopathological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants.     

Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines

The need for multiple vaccinations to enhance the immunogenicity of subunit vaccines may be reduced by delivering the vaccine over an extended period of time. Here, we report two novel injectable pentablock copolymer based thermoresponsive hydrogels made of polyethyleneglycol-polycaprolactone-polylactide-polycaprolactone-polyethyleneglycol (PEG-PCL-PLA-PCL-PEG) with varying ratios of polycaprolactone (PCL) and polylactide (PLA), as single shot sustained release vaccines. Pentablock copolymer hydrogels were loaded with vaccine-encapsulated poly lactic-co-glycolic acid nanoparticles (PLGA-NP) or with the soluble vaccine components. Incorporation of PLGA-NP into the thermoresponsive hydrogels increased the complex viscosity of the gels, lowered the gelation temperature, and minimized the burst release of antigen and adjuvants. The two pentablock hydrogels stimulated both cellular and humoral responses. The addition of PLGA-NP to the hydrogels sustained immune responses for up to 49 days. The polymer with a higher ratio of PCL to PLA formed a more rigid gel, induced stronger immune responses, and stimulated effective anti-tumor responses in a prophylactic melanoma tumor model.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-015-9843-4) contains supplementary material, which is available to authorized users.KEY WORDS: nanoparticles, pentablock copolymers, sustained release, thermoresponsive hydrogels, vaccine delivery     

Thermoresponsive Gelatin/Monomethoxy Poly(Ethylene Glycol)–Poly(d,l-lactide) Hydrogels: Formulation, Characterization, and Antibacterial Drug Delivery

Purpose The primary objective of this study was to prepare novel thermoresponsive binary component hydrogels composed of gelatin and monomethoxy poly(ethylene glycol)–poly(d,l-lactide) (MPEG–PDLLA) diblock copolymer and to obtain optimal formulations capable of forming gels upon a narrow temperature range between body temperature and room temperature. Methods MPEG–PDLLA diblock copolymers with a lower critical solution temperature (LCST) feature were synthesized by using a ring-opening polymerization method. The starting weight ratio of MPEG/DLLA was varied to obtain a series of copolymers with a wide range of molecular weight and hydrophilicity. The copolymers were characterized by ¹H nuclear magnetic resonance (¹H NMR) and thermogravimetric analysis. MPEG (2K)–PDLLA (1:4) was chosen to construct hydrogels with gelatin. To obtain optimal thermoresponsive formulation, various hydrogels were formulated and quantified in terms of sol–gel phase transition kinetics and rheological properties. Selected hydrogels were studied as drug carrier for gentamicin sulfate. Results Gelatin/MPEG–PDLLA hydrogels underwent gelation in less than 15 min when 30 wt.% MPEG (2K)–PDLLA (1:4) was mixed with 10, 50, or 100 mg/mL gelatin. Hydrogels showed rapid gelation when 100 mg/mL gelatin was mixed with 15, 20, or 25 wt.% MPEG–PDLLA as temperature fell from 37°C to room temperature. The viscosity of hydrogels depended on the frequency applied in the rheological tests, the environment temperature, and the concentration of both polymer components. The time needed for 50% gentamicin sulfate release was 5 days or longer at room temperature, and the release lasted up to 40 days. ¹H NMR confirmed that MPEG–PDLLA hydrolyzed under in vitro situations. Conclusions The incorporation of a second polymer component MPEG–PDLLA into the gelatin hydrogel could modify the thermal characteristic of gelatin and the resulting binary component hydrogels obtained different thermal characteristics from the individual polymer components. Formulation of gelatin/MPEG–PDLLA hydrogels could be varied for obtaining such gels that can undergo gelation promptly upon a narrow temperature change.     

可注射更昔洛韦温敏型原位凝胶剂的研究

构建温敏型三嵌段共聚物,研究其理化性质以及用其制备的可注射更昔洛韦温敏型原位凝胶剂的制剂特性。以聚乙二醇（PEG）作为亲水嵌段．丙交酯（LA）和β-丁内酯（β-BL）的无规共聚物PBLA作为疏水嵌段．采用开环聚合法合成温敏型三嵌段共聚物PBLA-PEG-PBLA,并对其理化性质进行表征,考察其溶液的胶凝温度／临界凝胶浓度、流变学性质、通针性和溶蚀行为以及以更昔洛韦作为模型药物、用其制得的可注射载药温敏型原位凝胶剂的体外释放特性。合成的PBLA-PEG-PBLA嵌段共聚物重均分子质量在6000左右,多分散系数为1．5左右;其溶液临界凝胶浓度（g·mL^-1）为5％-10％,质量浓度（g·mL^-1）在10％～25％时胶凝温度为31～35℃,接近并略低于体温：其凝胶在低温下储能模量与黏度较小,当温度接近相转变温度后两者迅速增大：其载药凝胶剂累计释放量经拟合显示遵循一级动力学方程,并呈扩散释药机制。较低质量浓度[10％15％（g·mL^-1）的PBLA—PEG—PBLA更符合玻璃体注射要求,更适用于制备可注射载药温敏型原位凝胶剂。     

Poly(lactide-co-glycolide) microparticles as systems for controlled release of proteins -- preparation and characterization

Poly(DL-lactide-co-glycolide) (PDLLGA) and poly(L-lactide-co-glycolide) (PLLGA) copolymers were prepared by bulk ring opening polymerization of lactide and glycolide and characterized by GPC, FTIR, 1H NMR and DSC. Copolymers with different molar masses at a constant lactide/glycolide ratio were used for preparation of bovine serum albumin (BSA)-loaded microparticles by the double emulsion w/o/w method. The influence of the copolymer molar mass and composition on the microparticle morphology, size, yield, degradation rate, BSA-loading efficiency and BSA release profile were studied. For microparticles prepared from PDLLGA copolymers, a biphasic profile for BSA release was found and for those made from PLLGA copolymers the release profile was typically triphasic; both of them were characterized by high initial burst release. Possible reasons for such behavior are discussed.     

Controlled release of lipase from Candida rugosa loaded into hydrogels of N-isopropylacrylamide and itaconic acid

The series of poly(N-isopropylacrylamide-co-itaconic acid) hydrogels, with lipase from Candida rugosa as a model protein, were synthesized by free radical copolymerization. The composition of hydrogels was varied by monomers ratio, crosslinking agent concentration and amounts of lipase, which was loaded by in situ polymerization. All samples were characterized regarding morphology. The investigation of hydrogel swelling properties revealed their pH and temperature sensitive character. Protein loading efficiency, release profiles and the specific activity yield of the released lipase were also investigated as a function of hydrogel composition, protein content and pH, at the physiological temperature of 37°C. Copolymers of N-isopropylacrylamide and itaconic acid presented high lipase loading efficiency. Another very important feature of these copolymers was that the protein release kinetic strongly depended on the pH value of the medium. The diffusion exponents values around 1 denoted that these hydrogel compositions could be adjusted to follow near zero-order kinetics. Namely, hydrogel formulations released low amounts of lipase at pH 2.20, but much higher released protein quantities were observed at pH 6.80 enabling these copolymers to be attractive candidates as site specific protein oral drug delivery systems.     

Gene Delivery to the Epidermal Cells of Human Skin Explants Using Microfabricated Microneedles and Hydrogel Formulations

Purpose Microneedles disrupt the stratum corneum barrier layer of skin creating transient pathways for the enhanced permeation of therapeutics into viable skin regions without stimulating pain receptors or causing vascular damage. The cutaneous delivery of nucleic acids has a number of therapeutic applications; most notably genetic vaccination. Unfortunately non-viral gene expression in skin is generally inefficient and transient. This study investigated the potential for improved delivery of plasmid DNA (pDNA) in skin by combining the microneedle delivery system with sustained release pDNA hydrogel formulations. Materials and Methods Microneedles were fabricated by wet etching silicon in potassium hydroxide. Hydrogels based on Carbopol polymers and thermosensitive PLGA-PEG-PLGA triblock copolymers were prepared. Freshly excised human skin was used to characterise microneedle penetration (microscopy and skin water loss), gel residence in microchannels, pDNA diffusion and reporter gene (β-galactosidase) expression. Results Following microneedle treatment, channels of approximately 150–200 μm depth increased trans-epidermal water loss in skin. pDNA hydrogels were shown to harbour and gradually release pDNA. Following microneedle-assisted delivery of pDNA hydrogels to human skin expression of the pCMVβ reporter gene was demonstrated in the viable epidermis proximal to microchannels. Conclusions pDNA hydrogels can be successfully targeted to the viable epidermis to potentially provide sustained gene expression therein.     

In situ gelling hydrogels incorporating microparticles as drug delivery carriers for regenerative medicine

Aqueous solutions of blends of biodegradable triblock copolymers, composed of poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) with varied D,L-lactide to glycolide ratios, displayed thermosensitivity and formed a gel at body temperature. The gel window of the blend solutions could be tuned by varying the blending ratio between the two components. Furthermore, the storage modulus of the resultant hydrogel from the copolymer blends at body temperature was higher than that of each individual component. Incorporation of poly(D,L-lactide) (PDLLA) microparticles (0.5-40% w/v) within the in situ gelling hydrogel did not change the sol-gel transition temperatures of the polymer solutions, while the mechanical strength of the resultant hydrogels was enhanced when the content of the microparticles was increased up to 30% and 40%. Incorporation of proteins into both the gel and microparticle components resulted in composites that controlled the kinetics of protein release. Protein within the gel phase was released over a 10-day period whilst protein in the microparticles was released over a period of months. This system can be used to deliver two drugs with differing release kinetics and could be used to orchestrate tissue regeneration responses over differing timescales.     

Triblock copolymers: synthesis, characterization, and delivery of a model protein

The purpose of this study was to synthesize and characterize biodegradable and thermosensitive triblock copolymers for delivering protein at controlled rate in biologically active form for longer duration of time. A series of thermosensitive triblock copolymers with different block lengths (PLGA-PEG-PLGA) were synthesized by ring-opening polymerization of d,l-lactide and glycolide with polyethylene glycol (PEG) in the presence of stannous octoate. Compositions and molecular weight of triblock copolymers were characterized by 1H NMR spectrometry and gel permeation chromatography, respectively. A single test-tube inverting method was employed to determine the sol-gel transition temperature. Lysozyme was used as a model protein. Lysozyme solution formulation was prepared with different triblock copolymers for in vitro release. Lysozyme concentration and its biological activity in the released sample were determined using a standard MicroBCA method and bacterial cell lysis method, respectively. The effects of varying block lengths and concentrations of copolymers on the in vitro release of lysozyme were evaluated. The release profiles from formulations showed a higher initial release followed by slower release up to 4 weeks. Increasing the block lengths of copolymers decreased burst release of lysozyme from 41.2+/-5.4% to 16.1+/-3.9%. Increasing copolymer concentrations decreased the drug release. Lysozyme in the 4 weeks released samples retained most of its biological activity (>80%). It is feasible to deliver protein in biologically active form for longer duration by varying block lengths and concentrations of triblock copolymers.     

Multi‐arm PEG/Silica Hydrogel for Sustained Ocular Drug Delivery

In the present study, a series of sustained drug delivery multiarm poly(ethylene glycol) (PEG)/silica hydrogels were prepared and characterizedThe hydrogels were formed by hydrolysis and condensation of poly(4‐arm PEG silicate) using the sol‐gel methodThe relationships between water content in the PEG/silica hydrogel and stability as well as rheological properties were evaluatedScanning electron microscopy analysis of the PEG/silica hydrogels revealed water content‐dependent changes in microstructureAn increase in water content resulted in larger pores within the hydrogel, longer gelation time and higher viscosityThe PEG/silica hydrogels were loaded with dexamethasone (DMS) or dexamethasone sodium phosphate (DMSP), drugs that are hydrophobic and hydrophilic in nature, respectivelyEvaluation of in vitro release revealed a zero‐order release profile for DMS over the first 6 days, suggesting that degradation of the silica hydrogel matrix was the primary mechanism of drug releaseIt was also found that the drug‐release profile could be tailored by varying the water content used during hydrogel preparationIn contrast, more than 90% of DMSP was released within 1 h, suggesting that DMSP release was only controlled by diffusionOverall, results from this study indicate that PEG/silica hydrogels may be promising drug‐eluting depot materials for the sustained delivery of hydrophobic, ophthalmic drugs© 2013 Wiley Periodicals, Incand the American Pharmacists Association J Pharm Sci 103:216–226, 2014     

用于关节腔注射的马钱子碱壳聚糖温敏凝胶的研究

利用壳聚糖-甘油-饱和硼砂溶液为主要材料构建一种用于关节腔注射、具有缓释作用的壳聚糖反相温敏水凝胶系统,并对其理化性质和生物相容性进行初步研究。以凝胶的形成和胶凝时间为指标,考察壳聚糖浓度、壳聚糖与甘油的比例、pH值等因素对水凝胶理化性质的影响,并对其体外释放行为、流变学、生物相容性等特性进行表征。温敏凝胶在常温下为溶胶态,当处于37℃时转变为凝胶态,并具有一定的缓释效果,生物相容性较高。     

Migration of marrow stromal cells in response to sustained release of stromal-derived factor-1α from poly(lactide ethylene oxide fumarate) hydrogels

Stromal derived factor-1α (SDF-1α) is an important chemokine in stem cell trafficking and plays a critical role in the homing of bone marrow stromal (BMS) cells. However, its use in tissue regeneration is limited by its relatively short half-life and the time-dependent nature of cell homing to the site of injury. The objective of this work was to investigate the release characteristics of SDF-1α from degradable poly(lactide ethylene oxide fumarate) (PLEOF) hydrogels and to determine the effect of sustained release of SDF-1α on migration of BMS cells. Three PLEOF hydrogels with poly(l-lactide) (PLA) fractions of 6%, 9%, and 24% by weight were synthesized. After the addition of chemokine, the polymerizing mixture was crosslinked to produce SDF-1α loaded PLEOF hydrogels. The hydrogels were characterized with respect to sol fraction, water uptake, degradation, SDF-1α loading efficiency and release kinetics, and migration rate of bone marrow stromal (BMS) cells. The more hydrophilic hydrogels with 6% and 9% PLA fraction had a pronounced burst release followed by a period of sustained release by diffusion for 21 days. The more hydrophobic hydrogel with 24% PLA fraction had a less pronounced burst release and displayed a slow but constant release by diffusion between days 1 and 9 followed by a fast release by diffusion-degradation from days 9 to 18. The fraction of active SDF-1α released from 6%, 9%, and 24% hydrogels after 21 days was 34.3%, 32.3%, and 35.8%, respectively. The migration of BMS cells in response to time-released SDF-1α closely followed the protein release kinetics from the hydrogels. The biodegradable PLEOF hydrogel may potentially be useful as a delivery matrix for sustained release of SDF-1α in the proliferative phase of healing for recruitment of progenitor cells in tissue engineering applications.     

Preparation and characterization of superporous hydrogels as gastroretentive drug delivery system for rosiglitazone maleate

BACKGROUND AND THE PURPOSE OF THE STUDY: Many drugs which have narrow therapeutic window and are absorbed mainly in stomach have been developed as gastroretentive delivery system. Rosiglitazone maleate, an anti-diabetic, is highly unstable at basic pH and is extensively absorbed from the stomach. Hence there is a need to develop a gastroretentive system. In this study a superporous hydrogel was developed as a gastroretentive drug delivery system. METHODS: Chitosan/poly(vinyl alcohol) interpenetrating polymer network type superporous hydrogels were prepared using a gas foaming method employing glyoxal as the crosslinking agent for Rosiglitazone maleate. Sodium bicarbonate was applied as a foaming agent to introduce the porous structure. Swelling behaviors of superporous hydrogel in acidic solution were studied to investigate their applications for gastric retention device. The optimum preparation condition of superporous hydrogels was obtained from the gelation kinetics. FT-IR, scanning electron microscopy, porosity and swelling ratio studies were used to characterize these polymers. In vitro drug release studies were also carried out. RESULTS: The introduction of a small amount of Poly(Vinyl Alcohol) enhanced the mechanical strength but slightly reduced the swelling ratio. The prepared superporous hydrogels were highly sensitive to pH of swelling media, and showed reversible swelling and de-swelling behaviors maintaining their mechanical stability. The degradation kinetics in simulated gastric fluid showed that it had biodegradability. Swelling was dependent on the amount of chitosan and crosslinker. The drug release from superporous hydrogels was sustained for 6 hrs. MAJOR CONCLUSION: The studies showed that chitosan-based superporous hydrogels could be used as a gastroretentive drug delivery system for rosiglitazone maleate in view of their swelling and prolonged drug release characteristics in acidic pH.