Cell Adhesive Character of Phenylboronic Acid-Modified Insulin and Its Potential as Long-Acting Insulin

Abstract

Phenylboronic acid (PBA) derivatives have attracted substantial attention owing to their unique character of forming dynamic covalent bonds with polyol compounds. Recent studies have shown interactions between PBA and sugar chains on the cell surface; they have interesting applications for sensors and drug delivery systems. In this study, we prepared phenylboronic acid-modified insulin (PBA-Ins) to evaluate its glucose-lowering activity and cell adhesiveness. In the case of intravenous injection, PBA-Ins showed longer glucose-lowering activity than native insulin. We hypothesized that this prolonged effect was the result of the interaction between the PBA moiety and sugar chains on the cell surface. Red blood cells (RBCs) were used as a cell model, and we confirmed PBA-Ins’s affinity for RBCs, which induced RBC agglutination. Interestingly, using an alternative PBA-Ins administration route markedly changed its glucose-lowering activity. Unlike the intravenous injection of PBA-Ins, the subcutaneous injection showed a small effect on glucose level, which indicated that a small amount of PBA-Ins was absorbed into the bloodstream. This suggested the importance of investigating the interaction between the PBA moiety and many types of cells, such as adipocytes, in subcutaneous tissues.

Preparation of Magnetic Hydrogel Microparticles with Cationic Surfaces and Their Cell-Assembling Performance

“…Moreover, a PBA group may be complexed with a polysaccharide chain located on the cell surface. 51,52 These may be possible explanations for this phenomenon. Figure 6 is a CLSM image of the cells after 30 min contact with various PVA(Fe)-PMTV hydrogel micro- particles.…”

“…In general, cationic polymers are able to interact with cell surfaces, and this phenomenon was observed in the case of the PVA­(Fe)-PMTV631 hydrogel microparticles. Moreover, a PBA group may be complexed with a polysaccharide chain located on the cell surface. , These may be possible explanations for this phenomenon. Figure is a CLSM image of the cells after 30 min contact with various PVA­(Fe)-PMTV hydrogel microparticles.…”

Bioresponsive Functional Phenylboronic Acid-Based Delivery System as an Emerging Platform for Diabetic Therapy

“…Using PBA to modify the cell adhesion of the drug prolongs the activity of the drug, because the PBA-modified drug may escape degradation and excretion, resulting in slow and long-lasting activity. Ohno et al 59 prepared PBA-modified insulin (PBA-Ins) and injected it intravenously into diabetic rats to evaluate the duration of their hypoglycemic activity; also, the study evaluated the difference between intravenous and subcutaneous injections. The results showed that PBA-Ins had longer hypoglycemic activity than natural insulin, as observed by monitoring the blood glucose levels.…”

Glucose and H2O2 Dual-Responsive Nanocomplex Grafted with Insulin Prodrug for Blood Glucose Regulation

“…The first one is artificial pancreatic device systems consisting of a glucose-monitoring sensor and an insulin infusion pump, while the poor biocompatibility and algorithm accuracy limit their application . The other one is chemical glucose response materials, mainly including glucose oxidase (GOx), , phenylboronic acid (PBA), , and glucose-binding proteins (GBP) . GBP mainly includes Con A, while the inherent limitations of Con A (poor biocompatibility and stability) lead to its less application. , GOx is a glucose-specific enzyme that catalyzes the oxidation of glucose into gluconic acid and generates hydrogen peroxide (H 2 O 2 ), while the byproduct H 2 O 2 can decrease the enzyme activity and damage the surrounding tissues and organs, and the release of GOx with carrier degradation may cause potential toxicity. − PBA can reversibly form boronic esters with cis -diol compounds and has good biocompatibility and stability, while PBA has low specificity and sensitivity to glucose .…”