In situ covalently cross-linked PEG hydrogel for ocular drug delivery applications

Avastin (R) has been clinically proved to be effective in the treatment of intraocular neovascularization diseases. However, the short half-life of Avastin (R) need frequent administration to maintain its therapeutic efficiency. In this paper, we attempted to develop an in situ PEG hydrogels with great biocompatibility for sustained release of Avastin (R) to inhibit the corneal neovascularization. PEG hydrogels was formed via thiol-maleimide reaction using 4-arm PEG-Mal and 4-arm PEG-SH. The transparent hydrogel was rapidly formed under physiological conditions. By varying the concentration of 4-arm PEG-SH, PEG hydrogel with different gelling time, pore size, swelling ratio and mechanical property could be obtained. In vitro cytotoxicity indicated that the developed PEG hydrogel had no apparent cytotoxicity on L-929 cells after 7 days of incubation. In vitro release study showed the encapsulated Avastin (R) was sustained release from PEG hydrogels within a period of 14 days study. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis further confirmed that the released Avastin (R) did not undergo apparent hydrolysis within 14 days. As a conclusion, we could conclude that the developed PEG hydrogels as an injectable hydrogels might be suitable for extended Avastin (R) release to treat the corneal neovascularization. (C) 2014 Elsevier B.V. All rights reserved.