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.
Highlights
Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia, which is considered a serious threat to human health [1,2,3]
A new glucose-responsive insulin delivery strategy was explored by formulating multivesicular liposome (MVL) sensitive to both pH and H2 O2
The local acidic and H2 O2 -enriched microenvironment is further induced by the in situ catalysis of glucose oxidase (GOx) under high glucose conditions; this destroys the outer MVL
Summary
Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia, which is considered a serious threat to human health [1,2,3]. Insulin is the only hypoglycemic hormone in the human body and is essential for the treating patients with diabetes to reduce blood glucose levels (BGLs) [5]. Compared with traditional insulin delivery systems, closed-loop insulin delivery systems can effectively regulate BGLs within the normal range. This type of system can discharge sufficient insulin during hyperglycemia and self-adjust to release a smaller insulin dose during normoglycemia; this is desirable for improving the quality of life of patients with diabetes [7]
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