Preparation of Thermosensitive Chitosan Formulations Containing 5-Fluorouracil/Poly-3-hydroxybutyrate Microparticles Used as Injectable Drug Delivery System  

作　　者：昝佳 朱德权 谭丰苹 蒋国强 林莹 丁富新 

机构地区：[1]Department of Chemical Engineering, Tsinghua University, Beijing 100084, China [2]School of Pharmacy, Tianjin University, Tianjin 300072, China

出　　处：《Chinese Journal of Chemical Engineering》2006年第2期235-241,共7页中国化学工程学报（英文版）

基　　金：Supported by the National Natural Science Foundation of China (No.20376038) and the Research Foundation of the Ministry ofEducation of China (No.2002003056).

摘　　要：The auto-gelling and drug release properties of the thermosensitive chitosan-β-glycerophosphate formulation were investigated. According to rheological study, gelation lag time of chitosan/β-glycerophosphate （GP） solutions varied from 2 to 60min with different deacetylation degree of chitosan, pH, gelation temperature, and the particles in the sol. The gelation properties were also found to influence the release profilles of a hydrophilic drug, 5-fluorouracil （5-FU）. Morphological examination by scanning electron microphotography demonstrated that large ＂pores＂ occurred during the gel-forming process, which created hydrophilic environment and led to the rapid initial release of the drug （85% in f＇LrSt 8h）. Poly-3-hydroxybutyrate （PHB）, a biodegradable material, was applied here as scaffold to capture 5-FU into microparticles with high encapsulation efficiency by solvent-nonsolvent method. Combination of these microparticles into the chitosan-β-GP formulation could drop the rapid initial release from 85% down to 29% in the optimized PHB content （75%, by mass）. The release could sustain for about 10 months. Tiffs study provided an understanding of the potential of injectable implant using thermosensitive chitosan-β-GP formulation containing PHB based particles for the water soluble drugs that need the property of long-term delivery.The auto-gelling and drug release properties of the thermosensitive chitosan-β-glycerophosphate for- mulation were investigated. According to rheological study, gelation lag time of chitosan/β-glycerophosphate (GP) solutions varied from 2 to 60min with different deacetylation degree of chitosan, pH, gelation temperature, and the particles in the sol. The gelation properties were also found to influence the release profiles of a hydrophilic drug, 5-fluorouracil (5-FU). Morphological examination by scanning electron microphotography demonstrated that large “pores” occurred during the gel-forming process, which created hydrophilic environment and led to the rapid initial release of the drug (85% in first 8h). Poly-3-hydroxybutyrate (PHB), a biodegradable material, was applied here as scaffold to capture 5-FU into microparticles with high encapsulation efficiency by solvent-nonsolvent method. Combination of these microparticles into the chitosan-β-GP formulation could drop the rapid initial release from 85% down to 29% in the optimized PHB content (75%, by mass). The release could sustain for about 10 months. This study provided an understanding of the potential of injectable implant using thermosensitive chitosan-β-GP formulation containing PHB based particles for the water soluble drugs that need the property of long-term delivery.

关 键 词：hydrogel CHITOSAN INJECTABLES MICROPARTICLE drug release 

分 类 号：TQ460.1[化学工程—制药化工]