Temperature-responsive and degradable hyaluronic acid/Pluronic composite hydrogels for controlled release of human growth hormone

Temperature-sensitive hyaluronic acid (HA) hydrogels were synthesized by photopolymerization of vinyl group modified HA in combination with acrylate group end-capped poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer (Pluronic F127). The synthesized HA/Pluronic composite hydrogels gradually collapsed with increasing temperature over the range of 5-40°C, suggesting that the Pluronic component formed self-associating micelles in the hydrogel structure. Upon prolonged incubation in a buffer medium, the micelles slowly degraded due to the hydrolytic scission of the ester linkage between the Pluronic and acrylate group. The mass erosion occurred much faster at 37°C than at 13°C, indicating that at the higher temperature, the ester linkage between the Pluronic and acrylate group might be more exposed to an aqueous environment and thus be more readily hydrolyzed due to Pluronic micellization. Incorporation of recombinant human growth hormone in the hydrogel resulted in a sustained release profile which followed a mass erosion pattern.