Thermosensitive poly(organophosphazene) hydrogels for a controlled drug delivery

Abstract

Thermosensitive poly(organophosphazenes) were synthesized for a controlled release of hydrophilic polymeric model drugs such as dextran and albumin in this study. The solutions of the present polymers bearing both hydrophobic side groups Of L-isoleucine ethyl ester (IleOEt) and hydrophilic groups of alpha-ammo-omega-methoxy-PEG (M-w 550) (AMPEG550) exhibited reversible sol-gel transition behaviors with changes of temperature. Viscometric measurement indicated that the thermosensitive hydrogels with good strength could be formed from the solutions in the range of the concentrations of 7-15 wt% around body temperature. For increasing their biodegradabililites, depsipeptides of ethyl-2-(O-glycyl)lactate (GlyLacOEt) were also introduced to the polymer, showing enhanced degradation of hydrogels. In vitro release behaviors of hydrophilic FITC-dextran (Mw 71,600) and human serum albumin from these polymer hydrogels were sustained for about 2 weeks while those from poloxamer (Pluronic F-127) hydrogel showed a distinct initial burst. The release of FITC-dextran exhibited concentration-dependent behavior ranging from 7 to 15 wt% of the polymer solution while it was almost independent of the concentration of FITC-dextran. (c) 2006 Elsevier B.V. All rights reserved.