Light-responsive coumarin-functionalised nanogels for metformin delivery

Abdelmohsen, Hend A.M. and Rochester, David L. and Kazlauciunas, Algy and Shaw, Elisabeth J. and Copeland, Nikki A. and Hardy, John G. (2025) Light-responsive coumarin-functionalised nanogels for metformin delivery. International Journal of Pharmaceutics, 684: 126109. ISSN 0378-5173

Abstract

Corneal neovascularization is one of the most severe ocular diseases. Current therapy is limited to repeated subconjunctival injections of antiangiogenic drugs, associated with significant side effects including infection, bleeding and erosive changes in the conjunctiva and sclera. Here, we describe the design of light-responsive nanogel-based drug delivery system using photocleavable coumarin-metformin conjugates. 18 different nanogel formulations were produced and triaged to 2 “optimal” formulations (CM9 and CM15) with sizes of ≈ 197–226 nm; the zeta potentials of CM9 and CM15 were –33.9 or −25.4 mV, respectively (i.e., electrically stabilized), and they were isolated in yields of 81 or 69 %, respectively. The drug loading in CM9 and CM15 nanogels was ≈ 71 or 78 µg/mg, respectively; and it was possible to deliver up to ≈ 92 % of the loaded metformin on demand with 6 rounds of light stimulation over 24 h. The metformin released in response to light exposure can suppress new blood vessel growth in vitro (using a HUVEC model). This study advances the development of minimally invasive photocleavable drug release systems for the treatment of ocular diseases.