A new class of biodegradable thermosensitive polymers. 2. Hydrolytic properties and salt effect on the lower critical solution temperature of poly(organophosphazenes) with methoxypoly(ethylene glycol) and amino acid esters as side groups

The hydrolytic properties of the novel biodegradable thermosensitive poly(organophosphazenes) with methoxypoly(ethylene glycol) (MPEG) and amino acid esters as side groups have been studied by means of gel permeation chromatography and P-31 and H-1 NMR spectroscopy and by identification of the hydrolysis products. The polymers substituted with alpha-amino acid esters were hydrolyzed faster than that with beta-amino acid ester. The higher content of the amino acid ester in the polymer backbone caused enhanced hydrolysis. The rate of the polymer degradation decreased in the order of methyl > ethyl > benzyl esters. The polymer hydrolysis occurred more rapidly in both acidic and basic buffer solutions than in the neutral solution. The P-31 NMR spectra of the polymers with high content of glycine ethyl ester showed that the polyphosphazene backbone underwent fragmentation mostly to small molecules after incubation in the buffer solution of pH 10 for 26 days. Phosphates and ammonia were formed as hydrolysis products in most cases. The hydrolytic behaviors of the present thermosensitive polyphosphazenes are consistent with the conventional acid-catalyzed degradation mechanism, and a detailed pathway to their hydrolytic degradation is proposed. The salt and pH effects on the thermosensitivity of the polymers were also examined by measuring their lower critical solution temperature (LCST) in aqueous solutions containing various inorganic and organic salts. When various inorganic salts were added to aqueous solutions of the polymers, their salting-in and salting-out effects were found to be mainly dependent on the anions of the salts. On the other hand, in the case of tetraalkylammonium halides which are organic salts, cations seem to play an important role: the salting-in effect is stronger with increasing alkyl chain of the ammonium salt. The aqueous solutions of the polymers showed higher LCST in the acidic solution than in the neutral and basic buffer solutions.