Prevention of corneal neovascularization by subconjunctival injection of avastin® loaded thermosensitive hydrogels in rabbit model

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Abstract

The antibody avastin® (Ava) has been clinically to treat various intraocular neovascular diseases, but suffering from the rapid clearance and short shelf-life of Ava in the requirement of frequent administration. In the present study, we reports the sustained release of Ava from a thermosensitive hydrogel based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PECE) copolymer for the control of corneal neovascularization in rabbit model. Ava were physically mixed with PECE aqueous solution at 4°C, and resulting Ava-PECE solution showed a sol-gel transition at physiological temperature (37°C). In vitro release study indicated that Ava-PECE hydrogel provided a sustained release of Ava up to 28days and the drug release behavior could be finely modulated by the change of PECE concentration. A single subconjunctival injection of PECE hydrogel hardly caused the change of intraocular pressure and corneal endothelial morphology during the entire study period. Intraocular pharmacokinetic analysis suggested that the Ava-PECE hydrogel provided a relatively higher Ava concentration in cornea over Ava solution up to 14days. In addition, anti-angiogenic effects of the Ava-PECE hydrogel in a suture-induced corneal neovascularization rabbit model indicated that the Ava-PECE hydrogel treatment exhibited superior anti-angiogenic efficacy over Ava solution treatment by decreasing the area ratio of neovascularization on 17days. Overall, the proposed Ava-PECE hydrogel acting a sustained drug delivery system might be a promising vehicle for the treatment of corneal neovascularization.

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