pH敏感的GMA修饰葡聚糖水凝胶的制备与体外释药研究

Preparation and in vitro evaluation of pH sensitive GMA-dextran hydrogels

目的:研究用于控释体系中的可生物降解的pH敏感水凝胶的制备方法及其智能释药特性.方法:过硫酸铵(APS)和四甲基乙二胺(TEMED)作引发体系,甲基丙烯酸缩水甘油酯(GMA)修饰的葡聚糖(GMA-dex)与丙烯酸(AAc)自由基共聚制备水凝胶.GMA-dex中GMA的取代度(DS)用核磁共振测定.在无酶的人工胃液与人工肠液中测定凝胶的平衡溶涨率,并分别测定载有平阳霉素的水凝胶在两种释放介质中的释药曲线.结果:GMA的取代度是10.5,凝胶在人工肠液中的溶涨率明显大于人工胃液,释放平阳霉素的速率也明显快于胃液.24h后,人工胃液与肠液中的累积药物释放率分别为22%和43%.结论:聚(GMA-dex/AAc)水凝胶的溶涨与释药具有pH敏感性.

AIM： To prepare the biodegradable pH-sensitive hydrogels for controlled drug delivery and to study its intelligent drug-release characteristics. METHODS： Hydrogels were obtained by radical copolymerization of aqueous solution of glycidyl methacrylate derivatived dextran （GMAdex） with acrylic acid （AAc） using ammonium peroxydisulfate （APS） and N, N, N, N-tetramethylethylenediamine （TEMED） as an initiation system. The degree of GMA substitution （DS） was determined by ^1H-NMR. The hydrogels were subjected to equilibrium swelling studies in enzymefree simulated gastric and intestinal fluids （SGF and SIF）. The release profiles of Pingyangmycin （PYM）-entrapped hydrogels in vitro were established in enzyme-free SGF and SIF. RESULTS： The DS of GMA was 10.5 and the swelling studies clearly indicated that these hydrogels were more swollen in SIF than those in SGF. The release of PYM from the hydrogels was much faster in SIF. After 24 h, about 22% and 43% of the entrapped drug were released in SGF and SIF, respectively. CONCLUSION： The swelling and drug release of Poly （GMA-dex/AAc） hydrogels are strongly dependent on the pH value.