Thermoresponsive gel for sustained release of BMP4 to inhibit corneal neovascularization

Abstract

This work aimed to seek a sustained drug release system based on poloxamer-based thermoresponsive gel for sustained release drugs to inhibit corneal neovascularization (CNV) after eye operations. Thus, we designed and prepared a thermoresponsive gel with a phase transition temperature from 22 °C to 25 °C. When the concentrations of poloxamer (P) was 18% (w/w) and ε-Polylysine (EPL) was 0.5 mg/mL (P-18-EPL-05) in the thermoresponsive gel solution, the obtained thermoresponsive gel showed a suitable viscosity and strength in physiological condition. The viscosity, storage modulus G' and loss modulus G" of P-18-EPL-05 were 8 × 10² mPa.s, 1.17 × 10⁴ Pa and 3.77 × 10³ Pa, respectively. In-vitro release studies indicated that the drug release ratio of P-18-EPL-05 gel better than that of the poloxamer solution alone. The animal experiments indicated that the thermoresponsive gel loading bone morphogenetic protein 4 (BMP4) was better to inhibit CNV than the common solvent one. Overall, these results demonstrated that P-18-EPL-05 gel would be a promising platform as drug sustained systems for inhibiting CNV after eye injury in ophthalmic applications.

Keywords: Bone morphogenetic protein 4; Corneal neovascularization; Phase transition; Sustained release; Thermoresponsive gel.