Hydrolytic degradation and protein release studies of thermogelling polyurethane copolymers consisting of poly[(R)-3-hydroxybutyrate], poly(ethylene glycol), and poly(propylene glycol)

This paper reports the hydrolytic degradation and protein release studies for a series of newly synthesized thermogelling tri-component multi-block poly(ether ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] (PHB), poly(propylene glycol) (PPG), and poly(ethylene glycol) (PEG). The poly(PEG/PPG/PHB urethane) copolymer hydrogels were hydrolytically degraded in phosphate buffer at pH 7.4 and 37 °C for a period of up to 6 months. The mass loss profiles of the copolymer hydrogels were obtained. The hydrogel residues at different time periods of hydrolysis were visualized by scanning electron microscopy, which exhibited increasing porosity with time of hydrolysis. The degradation products in the buffer were characterized by GPC, 1H NMR, MALDI-TOF, and TGA. The results showed that the ester backbone bonds of the PHB segments were broken by random chain scission, resulting in a decrease in the molecular weight. In addition, the constituents of degradation products were found to be 3-hydroxybutyric acid monomer and oligomers of various lengths (n=1–5). The protein release profiles of the copolymer hydrogels were obtained using BSA as model protein. The results showed that the release rate was controllable by varying the composition of the poly(ether ester urethane)s or by adjusting the concentration of the copolymer in the hydrogels. Finally, we studied the correlation between the protein release characteristics of the hydrogels and their hydrolytic degradation. This is the first example that such a correlation has been attempted for a biodegradable thermogelling copolymer system.