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

Avastin® has been clinically proved to be effective in the treatment of intraocular neovascularization diseases. However, the short half-life of Avastin® 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® 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® 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® 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® release to treat the corneal neovascularization.

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