瘤内注射用替加氟温敏凝胶的处方筛选及体外释放研究

Formula Screening and in vitro Drug Release of Tegafur Thermo-sensitive Gel for Intratumor Injection

目的:筛选瘤内注射用替加氟温敏凝胶的最佳处方并考察其体外释放特征。方法:通过细胞毒性试验确定药物剂量,以聚丙交酯-乙交酯-聚乙二醇-聚丙交酯-乙交酯(PLGA-PEG-PLGA)、羟丙基甲基纤维素(HPMC)为基质制备凝胶。以体外释放度为指标,考察不同浓度PLGA-PEG-PLGA和HPMC等因素对凝胶的影响,并以胶凝温度、黏度、pH等评价凝胶质量。结果:凝胶剂的最佳处方为:25%PLGA-PEG-PLGA,1%HPMC,替加氟剂量为1 mg·ml^(-1)。制得凝胶的平均胶凝温度为36.7℃,平均黏度为7 550 m Pa·s,平均pH为7.2。结论:所制备的瘤内注射用替加氟温敏凝胶具有温敏特性和明显的缓释作用,为后续的临床研究提供了试验依据。

Objective： To screen the best formula of tegafur temperature-sensitive gel for intratumor injection and investigate the in vitro drug release behavior. Methods： The drug dose was determined by cytotoxieity experiment. The thermo-sensitive gel was prepared with PLGA-PEG-PLGA and HPMC as the matrix. With the in vitro release as the index, the effects of PLGA-PEG-PLGA and HPMC at different concentrations on gel were investigated. The gelation temperature, viscosity and pH were detected. Results： The best formula was as follows： 25% PLGA-PEG-PLGA, 1% HPMC, and tegafur dose of 1 mg·ml^-1. The average gelation temperature was 36.7℃ , the average viscosity was 7550 mPa · s, and the average pH was 7.2. Conclusion ： Tegafur thermo-sensitive gel for intratumor injection shows temperature sensitivity and obvious sustained-release property, which provides experimental basis for the further clinical research.