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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Development of a Ranibizumab Biosimilar using Bovine Milk-Derived Exosomes for the Inhibition of Corneal Neovascularization

Author(s): Zhou-Nalei, Li-Yanchao, Qiao-Xinrui, Yang-Xinya, Ma-Siqi, Shi-Junfang and An-Jianbin*

Volume 20, Issue 9, 2023

Published on: 20 August, 2022

Page: [1308 - 1317] Pages: 10

DOI: 10.2174/1570180819666220620103339

Price: $65

Abstract

Introduction: Corneal neovascularization disease is an important clinical symptom of many ocular surface disorders, and the use of anti-Vascular Endothelial Growth Factor (anti- VEGF) drugs is considered the most promising treatment method.

Method: Ranibizumab (RB) is one of the few anti-VEGF drugs approved by the FDA in the treatment of ophthalmic diseases, but the special synthetic route leads to a short biological halflife, and therapeutic concentration cannot be maintained for a long time in clinical treatment. Therefore, we aimed to develop low immunogenicity sustained-release system to improve the bioavailability of RB. RB was loaded on bovine milk-derived exosomes (MEXOs), and the in vitro release profile and pharmacokinetic characteristics were detected. RB was continuously released from the MEXOs (2 days, 60 h). The tubular network formation experiment on human umbilical vein endothelial cells showed that the MEXOs enhanced the inhibitory effects of RB on VEGFinduced tube formation, as confirmed by a cell proliferation experiment.

Results: In vivo experiments showed that RB-loaded bovine milk-derived exosomes (RBMEXOs) increased the precorneal residence time and half-life period of RB in New Zealand white rabbits.

Conclusion: These results suggested that RB-MEXOs are conducive to maintaining effective RB concentration In vivo, and their use is a potential strategy for treating corneal vascularization.

Keywords: Ranibizumab, Milk-derived exosomes, Angiogenesis, Sustained release

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