Issue 11, 2019

Sustained delivery of anti-VEGFs from thermogel depots inhibits angiogenesis without the need for multiple injections

Abstract

Anti-vascular endothelial growth factor (anti-VEGF) proteins are the gold-standard treatment for posterior eye segment proliferative vascular diseases such as Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR). However, the standard of care requires inconvenient monthly intravitreal injections. This underlies an unmet clinical need to develop alternative solutions for sustained delivery of biologics. In this paper, we demonstrated that anti-VEGFs can be encapsulated by a simple mild process into our polyurethane thermogel depots. By changing the hydrophilic–hydrophobic balance in the copolymer, anti-VEGF release rates can be modulated. The antibody in the thermogel partitions into protein domains which vary in size corresponding to the hydrophilicity balance of the polymer. Anti-VEGFs can be released in a relatively linear manner from the thermogel for up to 40 days in vitro. The encapsulated anti-VEGFs demonstrate anti-angiogenic bioactivity by inhibiting vessel outgrowth in rat ex vivo choroidal explants, and reducing vascular leakage in a VEGF-driven neovascularization rabbit model. In conclusion, we show that these thermogels can be tuned in terms of hydrophilicity and used for sustained delivery of bioactive anti-VEGFs. Physically cross-linked polyurethane thermoresponsive hydrogels could be a promising platform for sustained delivery of biologically active therapeutic proteins.

Graphical abstract: Sustained delivery of anti-VEGFs from thermogel depots inhibits angiogenesis without the need for multiple injections

Supplementary files

Article information

Article type
Paper
Submitted
06 Jul 2019
Accepted
08 Aug 2019
First published
14 Aug 2019

Biomater. Sci., 2019,7, 4603-4614

Sustained delivery of anti-VEGFs from thermogel depots inhibits angiogenesis without the need for multiple injections

K. Xue, X. Zhao, Z. Zhang, B. Qiu, Q. S. W. Tan, K. H. Ong, Z. Liu, B. H. Parikh, V. A. Barathi, W. Yu, X. Wang, G. Lingam, W. Hunziker, X. Su and X. J. Loh, Biomater. Sci., 2019, 7, 4603 DOI: 10.1039/C9BM01049A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements