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

Enzymic hydrolyzed chitosan was employed to prepare chitosan-tripolyphosphate and chitosan-polyphosphoric acid gel beads using a polyelectrolyte complexation method for the sustained-release of anticancer agent, 6-mercaptopurine (6-MP). pH responsive swelling ability, drug-release characteristics, and morphology of the chitosan gel bead depends on polyelectrolyte complexation mechanism and molecular weight of the enzymic hydrolyzed chitosan. The complexation mechanism of chitosan beads gelled in pentasodium tripolyphosphate or polyphosphoric acid solution was ionotropic crosslinking or interpolymer complex, respectively. The drug-release patterns of all chitosan gel beads in pH 6.8 seemed to be diffusional based, which might be in accordance with the Higuchi model, whereas release profiles of the chitosan-tripolyphosphate gel beads in pH 1.2 medium seemed to be non-Fickian diffusion controlled due to the swelling or matrix erosion of the beads. The rate of 6-MP releasing from chitosan-tripolyphosphate or chitosan-polyphosphoric acid gel matrix were significantly increased with the decreased molecular weight of enzymic hydrolyzed chitosan. However, the dissolution rates of 6-MP entraped in chitosan-tripolyphosphate and chitosan-polyphosphoric acid gel matrix 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 simulated intestinal and gastric juice medium than the chitosan-tripolyphosphate gel beads.