聚缩酮PCADK的合成及胰岛素微球的制备与表征

Synthesis of polyketal-PCADK and preparation and characterization of insulin microspheres

目的:合成新型生物可降解材料聚缩酮(PCADK),制备胰岛素微球并研究其体外释放行为。方法:以1,4-环己烷二甲醇(CDM)和2,2-二甲氧基丙烷(DMP)为原料合成PCADK,1H NMR表征聚合物结构,凝胶渗透色谱法(GPC)测定聚合物相对分子质量;采用in-situ S/O/W法制备载药微球,HPLC检测计算微球载药量和包封率;并测定了微球在pH=2.0,4.5,7.4的磷酸盐缓冲溶液中的释放行为。结果:重均相对分子质量约为6 500;制备的微球外观圆整,表面有褶皱,载药量为3.90%,包封率达68.0%;体外释放结果显示,聚缩酮微球在酸性条件下降解较快,碱性及中性环境中降解缓慢。结论:新型高分子材料PCADK制备的胰岛素微球,球形好,载药量、包封率较高,体外释放行为显示出pH敏感特性。

Objective： To prepare insulin-loaded microspheres with a novel biodegradable material termed polyketal（ PCADK） and evaluate their release behavior in vitro. Methods： The polyketal（ PCADK） was synthesized by using 1,4-cyclohexanedimethanol（ CDM） and 2,2-dimethoxypropane（ DMP）. The chemical structure of PCADK was confirmed by 1H NMR and the molecular weights（ Mw） of the polymers were determined by gel permeation chromatography（ GPC）; the microspheres were fabricated through a new solvent evaporation process-in-situ S/O/W process. The drug loading and encapsulation efficiency were detected and calculated via HPLC; the release experiment of microspheres was conducted in phosphate buffer solution（ pH = 2. 0,4. 5,7. 4）. Results： A polymer with an Mwof approximately 6 500 was obtained; the prepared microspheres had round appearance and plicate surface with drug loading of about 3. 90% and encapsulation efficiency of 68%; the in vitro release experiments showed that the microspheres degraded faster in acid solution than that in alkaline and neutral environment. Conclusion：The microspheres prepared by the novel polymer material-PCADK have high drug loading and encapsulation efficiency as well as pH-sensitive release kinetics.