In vivo variable and multi-day response from an insulin-releasing photoactivated depot.
Document Type
Article
Publication Date
8-15-2023
Identifier
DOI: 10.1016/j.bmcl.2023.129388
Abstract
Previously we have demonstrated that light can be used to control the release of insulin in diabetic animals, followed by a reduction in blood glucose. This is accomplished using a photoactivated depot (PAD) of insulin injected into the skin, and irradiated by a small external LED light source. In this work for the first time we demonstrate dose-response, showing that we can vary insulin release and commensurate blood glucose reduction by varying the amount of light administered. In addition to demonstrating dose-response, we have shown multi-day depot response, with insulin being released on two different days from the same depot. The material used in these studies was CD-insulin, a form of insulin that has a highly non-polar cyclododecyl group attached, markedly reducing the solubility of the modified material, and allowing it to form a depot upon injection. Upon photolysis, the cyclododecyl group is removed, releasing fully native, soluble insulin. Variable response and multi-day response as demonstrated strongly support the potential utility of the PAD approach for the variable and extended release of therapeutic peptides.
Journal Title
Bioorganic & medicinal chemistry letters
Volume
92
First Page
129388
Last Page
129388
MeSH Keywords
Animals; Insulin; Blood Glucose; Skin; Solubility; Photolysis
Keywords
Insulin; Light activation; Photochemistry; Variable delivery
Recommended Citation
Nadendla K, Chintala S, Kover K, Friedman SH. In vivo variable and multi-day response from an insulin-releasing photoactivated depot. Bioorg Med Chem Lett. 2023;92:129388. doi:10.1016/j.bmcl.2023.129388
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Comments
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