氟尿嘧啶可降解微球-凝胶载药系统的构建

 目的构建以明胶-PLGA微球和壳聚糖/聚乙烯醇(PVA)凝胶为基础的氟尿嘧啶(5-Fu)复合微粒凝胶缓释系统。方法制备5-Fu明胶微球,采用O/O溶剂挥发法将微球包囊于PLGA内,考察复合微球的形态,粒径及体外释放。以冷冻-解冻循环法制备壳聚糖/PVA凝胶,将复合微球载入凝胶中,考察复合微粒凝胶系统的体外释放。结果复合微球外观圆整,包封率85%以上,增加PLGA浓度,降低明胶微球载药量可以减少体外突释量。对微球的体外释放曲线拟合结果表明,低载药量的微球释放符合零级释放方程,而载药量高的微球符合Higuchi方程。通过调节PLGA浓度可以控制释放速率。复合微粒凝胶系统的体外释放实验表明,微球的突释量随壳聚糖含量增加而减少。结论5-Fu明胶-PLGA复合微球包封率高,具有缓释控释的作用,载入壳聚糖/PVA凝胶后,改善复合微球的突释行为,此复合微粒凝胶缓释系统有望用于胃肠道腹腔化疗中。

Construction of 5-Fluorouracil Delivery System Based on Chitosan/Poly( Vinyl Alcohol) Complex Hydrogel with Built-in Composite Microspheres of Gelatin and PLGA

OBJECTIVE To develop a 5-fluorouracil(5-Fu) sustained delivery system based on chitosan/poly(vinyl alcohol)(PVA) complex hydrogel with built-in gelatin-PLGA composite microspheres.METHODS 5-Fu loaded gelatin microspheres were prepared by emulsification-chemical crosslinking method then incorporated into PLGA matrix by oil-in-oil emulsification extraction technique to obtain the composite microspheres.The shape,size,the encapsulation efficiency of 5-Fu,and in vitro drug release profiles of prepared microspheres were investigated.Chitosan/PVA hydrogels were prepared by freeze-thaw circle method.5-Fu release profiles from gelatin-PLGA microspheres entrapped in chitosan/PVA hydrogels were investigated.RESULTS The composite microspheres were in good shape and the encapsulation efficiency of 5-Fu was over 85%.The burst release was decreased while the polymer concentration was increased and drug loading was decreased.The in vitro release profile of 5-Fu composite microspheres with low drug content was fitted with first-order kinetic equation while that of 5-Fu composite microspheres with high drug content was discribed by Higuchi equation.Moreover,the release profiles were manipulated by regulating the concentration of PLGA in the composite microspheres.The burst effect was ameliorated by entrapping the composite microspheres into chitosan/PVA hydrogels.CONCLUSION By the combination of gelatin-PLGA composite microspheres and chitosan/PVA hydrogel,a controlled delivery system for 5-Fu was developed.This drug delivery system prepared by composite microspheres into chitosan/PVA hydrogels has the potential use in early entrapping intraperitoneal chemotherapy for advanced gastrointestinal carcinoma.