Thermo-Sensitive Release Behavior of 5-Fluorouracil from Chitosan-Gel Microspheres Coated with Lipid Multilayers

Abstract

In order to provide a device that would release anticancer drugs in response to temperature, chitosan microspheres with immobilized 1-[N-(5- aminopentyl)urea]-5-fluorouracil (Ap-5FU) and coated with dipalmitoyl phosphatidyl choline (DPPC) multilayers were prepared. The chitosan-DPPC- chitosan microspheres were prepared by coating chitosan-DPPC microspheres with polyelectrolyte complex membrane of chitosan. Good distributive stability of microspheres in aqueous solution was achieved with the DPPC multilayers coating. When chitosan was crosslinked with glutaraldehyde, Ap-5FU was si multaneously immobilized to the microspheres by means of Schiffs base forma tion. In physiological saline media, free 5FU released from the microspheres was detected, but the 5FU derivative was not. The release rate of 5 FU from the microspheres was decreased by coating with DPPC multilayers, and further depressed by the formation of polyelectrolyte complex membrane. The thermo- sensitive release behavior of 5FU from chitosan-DPPC microspheres and chitosan-DPPC-chitosan microspheres was observed in vitro across the phase transition temperature (T _m ) of the DPPC multilayer (41.4 ° C).