摘要
目的制备紫杉醇脂质体的PLGA-PEG-PLGA水凝胶,考察其在蛋白酶K作用下的释放行为。方法 干膜-水化法制备载紫杉醇的脂质体,合成质量嵌段比为1∶2∶1的PLGA-PEG-PLGA聚合物,将载药脂质体混合进聚合物水凝胶中,分别采用扫描电子显微镜和激光粒度测定仪观察其微观形态和测定其粒径,采用高效液相色谱法测定紫杉醇在含有蛋白酶K情况下的的释放行为。结果 载药脂质体在水凝胶中分布较均匀,脂质体凝胶中紫杉醇的释放行为呈现0级动力学,释放介质中蛋白酶K的存在可以加速紫杉醇的释放。水凝胶中包载的脂质体量对紫杉醇释放行为和速率影响不大。脂质体中紫杉醇的包裹量对其释放行为及速率无明显影响,脂质体的粒径较大时,释放速率及1周后的释放量稍小于较小粒径脂质体。药物在1周内释放基本完全。结论 紫杉醇的原位,0级,缓释给药可通过将其包裹在脂质体,再进一步包裹在生物可降解聚酯水凝胶中实现。释放介质中蛋白酶K的存在可加速但不改变其释放行为。
Objective To investigate the release behavior of paclitaxel under proteinase K after liposomal paclitaxel in PLGA -PEG -PLGA hydro -gel was prepared. Methods Liposomal paclitaxel was prepared by dry film -hydration meth- od and PLGA -PEG -PLGA polymer with mass ratio of 1： 2：1 was synthesized. Drug -loaded liposomes were mixed in poly- mer hydro - gel and scanning electron microscope and laser particle detector were used respectively to observe the morphology and to determine the particle - sizes. High performance liquid chromatography was used to determine the release profile of pa- clitaxel under proteinase K. Results Paclitaxel - loaded liposomes were evenly distributed in hydro - gel, and paclitaxel ex- hibited 0 - order release behavior. Proteinase K in release medium could accelerate the release speed of paclitaxel. The a- mounts of liposomes entrapped in hydro - gels had little effect on the release behavior and speed of paclitaxel. The amount of entrapped paelitaxel in liposomes had no obvious effect on the release behavior and speed of itself. As the particle - diameters of liposomes increased, paclitaxel release speed and release amount after 1 week were a little lower than those with smaller di- ameters. All samples released thoroughly by and large after 1 week. Conclusions Situ, 0 - order and sustained release of paclitaxel can be realized by being loaded into liposomes which are further loaded in biodegradable polyester hydro - gel. Pro- teinase K in release medium can accelerate their release speed without affecting release behavior.
出处
《辽宁医学院学报》
CAS
2013年第2期68-71,I0006,I0007,共6页
Journal of Liaoning Medical University (LNMU) Bimonthly
基金
辽宁医学院"博士及出国进修1年以上教师科研启动基金"资助项目
项目编号:Y2012B012
关键词
紫杉醇
脂质体
水凝胶
聚酯
嵌段共聚物
蛋白酶K
paclitaxel
liposome
hydro- gel
polyester
blocked copolymer
proteinase K
