氟尿嘧啶3种原位形成植入体的体外释放度研究

Studies on in vitro Release of Three In-situ Forming Implants Containing 5-Fluorouracil

目的:考察处方和制备工艺对氟尿嘧啶(5-FU)3种原位形成植入体释药速度的影响。方法:以单甲基聚乙二醇-羟基乙酸共聚物(mPEG-PLGA)为材料制备温敏性凝胶,以聚乙二醇/乳酸羟基乙酸共聚物(PLGA-PEG-PLGA)为材料制备原位形成凝胶剂,原位形成微球分别以PLGA-PEG-PLGA、聚乳酸(PLA)、端羧基聚乳酸-羟基乙酸共聚物(PLGA-C00H)为材料制备。采用UV法通过透析袋法测定体外释放度。结果:聚合物的浓度是影响原位植入体体外释放度的主要因素。除此外对于原位微球剂来说,N-甲基吡咯烷酮(NMP)和油相的比例也是影响体外释放度的重要因素之一。3种原位形成植入体主要通过扩散机制释药,其中温敏性凝胶的释药速度最快,原位微球剂与原位形成凝胶剂相比,突释减小,释药速度降低。结论:原位微球剂的控释效果最理想,值得进一步研究。

Objective： To examine the effects of formulation factors on in vitro release rate of three in-situ forming implants contai- ning 5-fluorouracil （5-FU）. Method： Thermosensitive hydrogel was prepared with mPEG-PLGA and in-situ forming hydrogel was pre- pared with PLGA-PEG-PLGA. Three kinds of polymers, namely PLGA-PEG-PLGA, PLA and PLGA-COOH were used to prepare in-situ forming microspheres. In vitro release rate was determined by UV through dialysis bag method. Result： The polymer concentration was the main factor to influence in vitro release of in-situ forming implants containing 5-FU. The volume ratio of NMP and oil phase was also the important factor to affect drug release rate of in-situ forming microspheres. Drug release from the three in-situ forming implants was accorded with diffusion mechanism. In vitro release rate of thermosensitive hydrogel was the quickest and in-situ forming microspheres had less burst-effect and more stable release rate compared with in-situ forming hydrogel. Conclusion： In-situ forming microspheres have more desirable controlled effects and are deserved to be investigated further.