Synthesis and characterization of biodegradable thermosensitive neutral and acidic poly(organophosphazene) gels bearing carboxylic acid group

Abstract

The needs to develop thermosensitive biodegradable polymers have been raised in the area of injectable polymer therapeutics. The aims of this work are to develop thermosensitive biodegradable poly(organophosphazene) gels having functional group and characterize their physicochemical properties such as thermosensitivity and hydrolytic behaviors. Controlled thermosensitivity and hydrolytic degradability of polymer gels were obtained with randomly grafted amphiphilic poly(organophosphazenes). Hydrophobic L-isoleucine ethyl ester (IleOEt) and hydrophilic poly(ethylene glycol) 550 or 750 Da (PEG 550 or 750) were substituted along with relatively small amount of glycylglycine allyl ester (GlyGlyOALL) which was deprotected into glycylglycine (GlyGlyOH). By this procedure several neutral (GlyGlyOALL) and acidic (GlyGlyOH) poly(organophosphazene) pairs with same substituent ratio were prepared, in which the ratio of substituent groups could systematically modulate their thermosensitive properties. The aqueous solutions and gels of prepared acidic poly(organophosphazene) also showed the thermosensitive sol-gel transition and biodegradation at body temperature, respectively. Acidic poly(organophosphazene) exhibited much faster hydrolytic degradation than neutral polymer in the buffer solutions (pH 7.4) at 37 A degrees C. With systematically regulated thermo-responsiveness and hydrolytic degradability, the synthesized poly(organophosphazenes) are expected to be smart injectable materials having a useful moiety and further chemically conjugated with various bioactive molecules for biomedical applications.