Injectable and thermosensitive poly(organophosphazene) hydrogels for a 5‐fluorouracil delivery

The drug solubility and its release profiles of an anticancer drug from an injectable thermosensitive poly(organophosphazene) hydrogel bearing hydrophobic L ‐isoleucine ethyl ester and hydrophilic α‐amino‐ω‐methoxy‐poly(ethylene glycol) with and without hydrolysis‐sensitive glycyl lactate ethyl ester or functional glycyl glycine have been investigated. 5‐Fluorouracil (5‐FU) was used as a model anticancer drug. The aqueous solutions of 5‐FU incorporated poly(organophosphazenes) were an injectable fluid state at room temperature and formed a transparent gel at body temperature. The poly(organophosphazene) solution could enhance the solubility of 5‐FU and its solubility (34.26 mg/mL) was increased up to 10‐fold compared to that in phosphate‐buffered saline (3.39 mg/mL, pH 7.4, 4°C). The in vitro drug release profiles from poly(organophosphazene) hydrogels were established in phosphate‐buffered saline at pH 7.4 at 37°C and the release of 5‐FU was significantly affected by the diffusion‐controlled stage. The results suggest that the injectable and thermosensitive poly(organophosphazene) hydrogel is a potential carrier for 5‐FU to increase its solubility, control a relatively sustained and localized release at target sites and thus decrease systemic side effects. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009