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

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 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.