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Controlled release bevacizumab in thermoresponsive hydrogel found to inhibit angiogenesis

Issue title: Frontiers in Biomedical Engineering and Biotechnology – Proceedings of the 3rd International Conference on Biomedical Engineering and Biotechnology, 25–28 September 2014, Beijing, China

Article type: Research Article

Authors: Hu, Chao-Chien; | Chaw, Jen-Ray | Chen, Chin-Fu | Liu, Hsia-Wei;

Affiliations: Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan | School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan | Graduate Institute of Applied Science and Engineering, Fu Jen Catholic University, New Taipei City, Taiwan | Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan | Department of Life Science, Fu Jen Catholic University, New Taipei City, Taiwan

Note: [] Corresponding author: Hsia-Wei Liu, Department of Life Science, Fu Jen Catholic University, No. 510, Jhongiheng Rd., Sinjhuang Dist., New Taipei City 24205, Taiwan. Tel.: +886-2-29053740; Fax: +886-2-29052193; E-mail: [email protected].

Keywords: Bevacizumab, thermo-responsive hydrogel, drug delivery system, angiogenesis

DOI: 10.3233/BME-141003

Journal: Bio-Medical Materials and Engineering, vol. 24, no. 6, pp. 1941-1950, 2014

Published: 2014
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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.

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