Effect of chitosan on the release of protein from thermosensitive poly(organophosphazene) hydrogels

Poly(organophosphazenes) have been suggested as a potential thermosensitive hydrogel for use in the development of an injectable gel-depot system. Under biological conditions, hydrophilic model protein drugs, including bovine serum albumin (BSA), gelatin type B (MW 20,000) (GB20), and fluorescein isothiocyanate albumin (FITC-albumin) loaded in the hydrogels were released for 1-2 weeks, showing an initial burst release. However, this initial burst release could be suppressed when the proteins were couched in a complex with chitosan, and under these conditions evidenced a prolonged release period. BSA, GB20, and FITC-albumin, all of which are negatively charged at a pH of 7.4, interacted with chitosan harboring positive amine groups. The formation of these protein/chitosan complexes were confirmed via measurements of changes in zeta-potential and high-performance liquid chromatography. We determined the appropriate ratio of proteins to chitosan for suppression of the initial burst to be 1:5 to 1:10. From these findings, we were able to conclude that both the release rate and release period could be controlled via the formation of protein/chitosan complex.