Results
Title

Glucose‐Responsive Charge‐Switchable Lipid Nanoparticles for Insulin Delivery.

Authors

Liu, Yun; Wang, Yanfang; Yao, Yuejun; Zhang, Juan; Liu, Wei; Ji, Kangfan; Wei, Xinwei; Wang, Yuanwu; Liu, Xiangsheng; Zhang, Shiming; Wang, Jinqiang; Gu, Zhen

Abstract

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.

Subjects

CATIONIC lipids; INSULIN; LIPIDS; HYPERGLYCEMIA; DRUG delivery systems; NANOPARTICLES; BLOOD sugar

Publication

Angewandte Chemie, 2023, Vol 135, Issue 20, p1

ISSN

0044-8249

Publication type

Academic Journal

DOI

10.1002/ange.202303097