pH敏感GMA修饰葡聚糖水凝胶制备及体外释药探究.docVIP

pH敏感GMA修饰葡聚糖水凝胶制备及体外释药探究 　 作者：吴红，张镇西，吴道澄，任波，苏丹 【关键词】 药物释放 Preparation and in vitro evaluation of pH sensitive GMAdextran hydrogels 　　【Abstract】 AIM: To prepare the biodegradable pHsensitive hydrogels for controlled drug delivery and to study its intelligent drugrelease 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,Ntetramethylethylenediamine (TEMED) as an initiation system. The degree of GMA substitution (DS) was determined by 1HNMR. 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 enzymefree 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 (GMAdex/AAc) hydrogels are strongly dependent on the pH value. 　　【Keywords】 dextran; acrylic acid; hydrogels; pHsensitive; swelling; drug release 　　【摘要】 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(GMAdex)与丙烯酸(AAc)自由基共聚制备水凝胶. GMAdex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. 24 h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(GMAdex/AAc)水凝胶的溶涨与释药具有pH敏感性. 　　【关键词】 葡聚糖；丙烯酸；水凝胶；pH敏感；溶涨；药物释放 　　0引言 　　水凝胶具有良好的物理化学性质和生物相容性，与疏水聚合物相比，水凝胶与被固定在其中的药物或生物活性分子的相互作用极其微小，可使被固定的物质长时间的保持活性. 因此水凝胶在药物控制释放等领域有着广泛的应用. 特别是环境敏感水凝胶作为智能聚合物为设计和制备自调式给药系统和生物工程方面的多种新应用提供了可行性［1］. 它们的特点是随着温度、pH值、离子强度及超声波等外界标志的微小变化，多孔凝胶的相体积会发生较大变化，内含物的释放速度急剧变化，而一旦标志物恢复，相体积与内含物释放速度也恢复原状，此即智能化可逆性响应. 甲基丙烯酸缩水甘油酯（