One-Year Ultralong Intravitreal Release of Tyrosine Kinase Inhibitor from Supramolecular Temperature-Responsive Hydrogel

One-Year Ultralong Intravitreal Release of Tyrosine Kinase Inhibitor from Supramolecular Temperature-Responsive Hydrogel

Biomacromolecules

10.1021/acs.biomac.5c01212

https://doi.org/10.1021/acs.biomac.5c01212

Xinxin Zhao, Qianyu Lin, Ivan Seah, Queenie Shu Woon Tan, Rubayn Zhi Rong Goh, Karishma N. Mehta, Zengping Liu, Abigail Tan, Sheen Enn Ariel How, Belynn Sim, Pablo Mota-Santiago, Nigel Kirby, Yihao Leow, Chen Chuan Lim, Yi Jian Boo, Shermin S. Goh, Jason Y. C. Lim, Xian Jun Loh, Xinyi Su

General Biochemistry, General Materials Science

14 November 2025

Zhao, X., Lin, Q., Seah, I., Tan, Q. S. W., Goh, R. Z. R., Mehta, K. N., Liu, Z., Tan, A., How, S. E. A., Sim, B., Mota-Santiago, P., Kirby, N., Leow, Y., Lim, C. C., Boo, Y. J., Goh, S. S., Lim, J. Y. C., Loh, X. J., & Su, X. (2025). One-Year Ultralong Intravitreal Release of Tyrosine Kinase Inhibitor from Supramolecular Temperature-Responsive Hydrogel. Biomacromolecules, 26(12), 8452–8464. https://doi.org/10.1021/acs.biomac.5c01212

Retinal neovascular diseases, a leading cause of blindness, can be treated with intravitreal tyrosine kinase inhibitors (TKIs). Injectable intravitreal depots capable of sustained TKI release for more than 6 months are highly desirable. While existing platforms utilize covalently cross-linked hydrogels for prolonged release, thermoreversible hydrogels with good injectability have been deemed unsuitable for long-duration drug delivery due to rapid erosion from weak physical cross-linking. Here, we report the first injectable supramolecular hydrogel capable of 1-year sustained TKI release, prepared by codissolving an amphiphilic thermogel with the TKI. This hydrogel achieved a 12-fold longer drug-release duration compared to commercial Pluronic-F127 thermogel, arising from strong polymer-drug interactions resulting in a distinct gel microstructure and enhanced persistence. The released TKI retained bioactivity after one year, successfully resolving choroidal neovascularization (CNV) lesions in murine models. Our findings highlight the potential of supramolecular hydrogels for ultralong drug delivery to the retina.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This research / project is supported by the A*STAR - Industry Alignment Fund - Pre-Positioning: Ocular Biomaterials for Vitreoretinal Therapeutic Applications
Grant Reference no. : H20c6a0033

This research / project is supported by the National Research Foundation - National Research Foundation Investigatorship - Thermogels for Therapeutic Applications
Grant Reference no. : NRF-NRFI07−2021−0003

This research / project is supported by the National Medical Research Council - Clinician Scientist Award
Grant Reference no. : MOH-001106

This research / project is supported by the A*STAR - Central Research Fund
Grant Reference no. :

https://oar.a-star.edu.sg/communities-collections/articles/22760

1525-7797
1526-4602

Institute of Materials Research and Engineering

https://doi.org/10.1021/acs.biomac.5c01212