Oral delivery of insulin with intelligent glucose-responsive switch for blood glucose regulation

Abstract

Background: The traditional treatment for diabetes usually requires frequent insulin injections to maintain normoglycemia, which is painful and difficult to achieve blood glucose control. Results: To solve these problems, a non-invasive and painless oral delivery nanoparticle system with bioadhesive ability was developed by amphipathic 2-nitroimidazole-l-cysteine-alginate (NI-CYS-ALG) conjugates. Moreover, in order to enhance blood glucose regulation, an intelligent glucose-responsive switch in this nanoparticle system was achieved by loading with insulin and glucose oxidase (GOx) which could supply a stimulus-sensitive turnover strategy. In vitro tests illustrated that the insulin release behavior was switched "ON" in response to hyperglycemic state by GOx catalysis and "OFF" by normal glucose levels. Moreover, in vivo tests on type I diabetic rats, this system displayed a significant hypoglycemic effect, avoiding hyperglycemia and maintaining a normal range for up to 14 h after oral administration. Conclusion: The stimulus-sensitive turnover strategy with bioadhesive oral delivery mode indicates a potential for the development of synthetic GR-NPs for diabetes therapy, which may provide a rational design of proteins, low molecular drugs, as well as nucleic acids, for intelligent releasing via the oral route.

In vivo oral insulin delivery via covalent organic frameworks

“…The use of nanoparticles can improve the transporting ability of proteins through the intestinal wall while protecting them against degradation in gastric uid. 80,81 TTA-DFP-nCOF/insulin-FITC transportation across the intestinal wall was assessed by measuring the apparent permeability using an ex vivo technique in excised rat small intestine using the non-everted mouse small intestine sac model. 82,83 The transportation of TTA-DFP-nCOF/insulin from the mucosal side to the serosal side of the non-everted mouse small intestine sac was measured and quantied by uorescence measurements.…”

Layered Double Hydroxide Modified with Deoxycholic and Hyaluronic Acids for Efficient Oral Insulin Absorption

“…16,17 However, due to insufficient surface stability, the original nanoparticles are often unstable in vivo. 18,19 A previous study showed that the expression modification of LDH improves its efficiency and controls the duration of action of a drug, 5 which is of major importance for our study with regard to improving insulin absorption. The unique transmembrane transport pathway and targeted transport characteristics of cholic acid render it possible to modify LDH with DCA.…”

A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

“…This is due to the advent of novel delivery systems that allow oral insulin to resist degradation in the GIT, be transported into circulation, and then act when desired depending on plasma glucose concentration, which is desirable given the complications associated with multiple daily invasive insulin injections. 246–249 Modulating GLP-1R activity is the most recent therapy used to treat T2D. 3 The first therapy is based on the use of DPP-IV inhibitors to delay GLP-1 breakdown from its active to inactive form.…”

“…94,105,106,111,[192][193][194][195]206,214,[219][220][221][222]225,228,232,241,[326][327][328]331 Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2021:14 circulation, and then act when desired depending on plasma glucose concentration, which is desirable given the complications associated with multiple daily invasive insulin injections. [246][247][248][249] Modulating GLP-1R activity is the most recent therapy used to treat T2D. 3 The first therapy is based on the use of DPP-IV inhibitors to delay GLP-1 breakdown from its active to inactive form.…”