Multivesicular Liposomes for Glucose-Responsive Insulin Delivery

Abstract

An intelligent insulin delivery system is highly desirable for diabetes management. Herein, we developed a novel glucose-responsive multivesicular liposome (MVL) for self-regulated insulin delivery using the double emulsion method. Glucose-responsive MVLs could effectively regulate insulin release in response to fluctuating glucose concentrations in vitro. Notably, in situ released glucose oxidase catalyzed glucose enrichment on the MVL surface, based on the combination of (3-fluoro-4-((octyloxy)carbonyl)phenyl)boronic acid and glucose. The outer MVL membrane was destroyed when triggered by the local acidic and H2O2-enriched microenvironment induced by glucose oxidase catalysis in situ, followed by the further release of entrapped insulin. Moreover, the Alizarin red probe and molecular docking were used to clarify the glucose-responsive mechanism of MVLs. Utilizing chemically induced type 1 diabetic rats, we demonstrated that the glucose-responsive MVLs could effectively regulate blood glucose levels within a normal range. Our findings suggest that glucose-responsive MVLs with good biocompatibility may have promising applications in diabetes treatment.

Current Technologies for Managing Type 1 Diabetes Mellitus and Their Impact on Quality of Life—A Narrative Review

“…To diminish the unwanted complications of insulin administration and increase the patient’s compliance, various research teams tried to incorporate it in multiple carriers for oral administration [ 146 , 147 , 148 ]: liposomes [ 149 , 150 ] mixed micelles [ 151 , 152 ], nanoparticles [ 153 , 154 , 155 ], intestinal patches [ 156 ]. Current studies also explore other access ways for insulin administration: intranasal [ 157 , 158 , 159 ], transdermal [ 160 , 161 ], and sublingual [ 162 , 163 ].…”

Glucose‐Responsive Charge‐Switchable Lipid Nanoparticles for Insulin Delivery

“…Several glucose‐responsive insulin formulations with improved BG control capability have been developed [5] . The carriers in these formulations were mainly developed from polymers, and glucose oxidase was generally incorporated as a glucose‐sensing moiety [5a, 6] . Polymers are associated with polydispersity in chemical structures while glucose oxidase released in vivo is toxic.…”