Final published version
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Light-responsive coumarin-functionalised nanogels for metformin delivery
AU - Abdelmohsen, Hend A.M.
AU - Rochester, David L.
AU - Kazlauciunas, Algy
AU - Shaw, Elisabeth J.
AU - Copeland, Nikki A.
AU - Hardy, John G.
PY - 2025/8/24
Y1 - 2025/8/24
N2 - 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.
AB - 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.
KW - Light-responsive
KW - Light-triggered
KW - Ocular drug delivery
KW - Photochemistry
KW - Stimuli-responsive
U2 - 10.1016/j.ijpharm.2025.126109
DO - 10.1016/j.ijpharm.2025.126109
M3 - Journal article
AN - SCOPUS:105014787435
VL - 684
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 126109
ER -