title: Controlled release bevacizumab in thermoresponsive hydrogel found to inhibit angiogenesis.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Chao-Chien
authors.initials: CC
authors.lastname: Hu
authors.affiliation: Graduate Institute of Applied Science and Engineering, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Jen-Ray
authors.initials: JR
authors.lastname: Chaw
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Chen
authors.affiliation: Department of Life Science, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Hsia-Wei
authors.initials: HW
authors.lastname: Liu
mesh_terms: D065966:Absorption, Physicochemical; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis*; D004058:Diffusion; D006358:Hot Temperature; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D013696:Temperature; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D003692:Delayed-Action Preparations; D020100:Hydrogels; D000068258:Bevacizumab
keywords: Bevacizumab; angiogenesis; drug delivery system; thermo-responsive hydrogel