Chitosan-polyelectrolyte complexation for the preparation of gel beads andcontrolled release of anticancer drug. I. Effect of phosphorous polyelectrolyte complex and enzymatic hydrolysis of polymer

Enzymic hydrolyzed chitosan was employed to prepare chitosan-tripolyphospha te and chitosan-polyphosphoric acid gel beads using a polyelectrolyte compl exation method for the sustained-release of anticancer agent, 6-mercaptopur ine (6-MP). pH responsive swelling ability, drug-release characteristics, a nd morphology of the chitosan gel bead depends on polyelectrolyte complexat ion mechanism and molecular weight of the enzymic hydrolyzed chitosan. The complexation mechanism of chitosan beads gelled in pentasodium tripolyphosp hate or polyphosphoric acid solution was ionotropic crosslinking or interpo lymer complex, respectively. The drug-release patterns of all chitosan gel beads in pH 6.8 seemed to be diffusional based, which might be in accordanc e with the Higuchi model, whereas release profiles of the chitosan-tripolyp hosphate gel beads in pH 1.2 medium seemed to be non-Fickian diffusion cont rolled due to the swelling or matrix erosion of the beads. The rate of 6-MP releasing from chitosan-tripolyphosphate or chitosan-polyphosphoric acid g el matrix were significantly increased with the decreased molecular weight of enzymic hydrolyzed chitosan. However, the dissolution rates of 6-MP entr aped in chitosan-tripolyphosphate and chitosan-polyphosphoric acid gel matr ix were significantly slower than the dissolution rate of the original drug . These results indicate that the chitosan-polyphosphoric acid gel bead is a better polymer carrier for the sustained release of anticancer drugs in s imulated intestinal and gastric juice medium than the chitosan-tripolyphosp hate gel beads. (C) 1999 John Wiley & Sons, Inc.