Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 62, Issue 20, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202303097
Keywords
Diabetes; Drug Delivery; Glucose-Responsive; Insulin Delivery; Lipid Nanoparticles
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Lipid nanoparticle-based drug delivery systems have a significant impact on nucleic acid-based therapy and vaccination. We designed phenylboronic acid-based quaternary amine-type cationic lipids that can self-assemble into spherical lipid nanoparticles. Mixing insulin with the lipid nanoparticles immediately forms a heterostructured insulin complex, and in a hyperglycemia-relevant glucose solution, the lipid nanoparticles gradually become less positively charged, leading to insulin release.
Lipid nanoparticle-based drug delivery systems have a profound clinical impact on nucleic acid-based therapy and vaccination. Recombinant human insulin, a negatively-charged biomolecule like mRNA, may also be delivered by rationally-designed positively-charged lipid nanoparticles with glucose-sensing elements and be released in a glucose-responsive manner. Herein, we have designed phenylboronic acid-based quaternary amine-type cationic lipids that can self-assemble into spherical lipid nanoparticles in an aqueous solution. Upon mixing insulin and the lipid nanoparticles, a heterostructured insulin complex is formed immediately arising from the electrostatic attraction. In a hyperglycemia-relevant glucose solution, lipid nanoparticles become less positively charged over time, leading to reduced attraction and subsequent insulin release. Compared with native insulin, this lipid nanoparticle-based glucose-responsive insulin shows prolonged blood glucose regulation ability and blood glucose-triggered insulin release in a type 1 diabetic mouse model.
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