Controlled release bevacizumab in thermoresponsive hydrogel found to inhibit angiogenesis.
Age-related macular degeneration (ARMD) and intraocular neovascular diseases have been treated clinically by anti-VEGF antibody drug bevacizumab. However, the use of bevacizumab in the treatment of retinal neovascular diseases has been limited due to the short half-life and frequent injections. In this research, novel amphiphilic hydrophilic-hydrophobic block copolymers of methoxy-poly (ethylene glycol)-block-poly (lactic-co-glycolic acid) were synthesized with ring-opening polymerization, and cross-linked with 2,2-bis (2-oxazoline) (BOX). The aqueous solution of the block copolymers can reverse the sol-gel-sol phase transition. After 1 month of intravitreal injection, the histomorphology of a rabbit's retina was preserved, which indicated the mPEG-PLGA-BOX hydrogel had no cytotoxicity in vivo. Released bevacizumab from the mPEG-PLGA-BOX hydrogel inhibited the RF/6A (Maraca mulatta retina epithelial cell) and HUVEC cell growth, and anti-angiogenesis in 3-D cultures, which showed the bioactivity of the anti-VEGF agent, were maintained in the hydrogel within the release process. In conclusion, the mPEG-PLGA-BOX hydrogel had a sol-gel behavior phase transition, and its intraocular biocompatibility and the characteristics of biodegradability and bioactivity appear to be a promising intravitreal injection carrier for bevacizumab delivery.
['Hu|Chao-Chien|CC|', 'Chaw|Jen-Ray|JR|', 'Chen|Chin-Fu|CF|', 'Liu|Hsia-Wei|HW|']
D065966:Absorption, Physicochemical D020533:Angiogenesis Inhibitors D000818:Animals D061067:Antibodies, Monoclonal, Humanized D000068258:Bevacizumab D020256:Choroidal Neovascularization D003692:Delayed-Action Preparations D004058:Diffusion D006358:Hot Temperature D006801:Humans D020100:Hydrogels D009389:Neovascularization, Pathologic D011817:Rabbits D013696:Temperature D016896:Treatment Outcome
Bevacizumab angiogenesis drug delivery system thermo-responsive hydrogel