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 alpha-amino-omega-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 degrees C). The hi vitro drug release profiles from poly(organophosphazene) hydrogels were established in phosphate-buffered saline at pH 7.4 at 37 degrees 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. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 113: 3831-3839, 2009