Glucose‐Responsive Charge‐Switchable Lipid Nanoparticles for Insulin Delivery

Abstract

Lipid nanoparticle-based drug delivery systems have a profound clinical impact on nucleic acidbased therapy and vaccination. Recombinant human insulin, a negatively-charged biomolecule like mRNA, may also be delivered by rationally-designed positivelycharged 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 selfassemble 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.People with type 1 diabetes require daily multiple injections of fast-acting insulin and one or two injections of longacting insulin or receive continuous insulin infusion via a pump to maintain their blood glucose (BG) normal. [1]

Spatiotemporal Immunomodulation and Biphasic Osteo‐Vascular Aligned Electrospun Membrane for Diabetic Periosteum Regeneration

“…Lipid nanoparticle‐based drug delivery systems have profound implications for diabetic‐based tissue damage repair. [ 55 , 57 ] Liposomes are nanocarriers that protect the active ingredients they carry from degradation. [ 58 ] They are currently considered the most successful drug carrier systems.…”

Lipoic acid-mediated oral drug delivery system utilizing changes on cell surface thiol expression for the treatment of diabetes and inflammatory diseases

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Selective organ targeting nanoparticles: from design to clinical translation

“…7A). 90 They formed an LNP complex from phenylboric acid-modified quaternary ammonium cationic lipids with negatively charged recombinant human insulin. When encountered with a high concentration of glucose, the decrease of positive charge of nanoparticles triggered insulin release.…”