Boronic Acid as Glucose-Sensitive Agent Regulates Drug Delivery for Diabetes Treatment

Abstract

In recent years, glucose-sensitive drug delivery systems have attracted considerable attention in the treatment of diabetes. These systems can regulate payload release by the changes of blood glucose levels continuously and automatically with potential application in self-regulated drug delivery. Boronic acid (BA), especially phenylboronic acid (PBA), as glucose-sensitive agent has been the focus of research in the design of glucose-sensitive platforms. This article reviews the previous attempts at the developments of PBA-based glucose-sensitive drug delivery systems regarding the PBA-functionalized materials and glucose-triggered drug delivery. The obstacles and potential developments of glucose-sensitive drug delivery systems based on PBA for diabetes treatment in the future are also described. The PBA-functionalized platforms that regulate drug delivery induced by glucose are expected to contribute significantly to the design and development of advanced intelligent self-regulated drug delivery systems for treatment of diabetes.

Boronic acids as building blocks for the construction of therapeutically useful bioconjugates

“…93 This technology could be the starting point for an interesting new concept for treatment of type II diabetes patients where a release of monomeric insulin (active form) occurs in response to an increase in serum carbohydrate concentration. 94,95 Similar strategies have been used to block the adhesion of cells to biological or biomedical surfaces by introducing PBA warheads onto a PEGylated polymer. In this approach, the PBA acts as a sugar-binding motif for carbohydrates on the cell surface (or hydroxyl groups on the surfaces of biomedical materials), while the PEG creates a hindered coating around the surface that blocks cell adhesion.…”

A boronic acid-based fluorescent hydrogel for monosaccharide detection

“…The saccharide-binding properties of aryl boronic acid derivatives have been exploited as recognition motifs across a number of different domains including polymer hydrogels [6,17,18]. Hydrogels are three dimensionally cross-linked hydrophilic polymers, with a high (~90 wt-%) water content [19].…”

Biologically Inspired and Chemically Derived Methods for Glucose‐Responsive Insulin Therapy

“…The cross‐links themselves are typically boronate esters that arise from simultaneous conjugation of covalently presented diol‐bearing moieties and PBAs. This approach can be accomplished through the inclusion of both subunits as pendant groups on the same polymer or by functional attachments to separate polymers that are then mixed . Phenylboronic esters, a class of PBA derivatives, are known to demonstrate peroxide‐sensitive degradation behavior, and have been exploited in some systems to drive insulin release dependent on the H 2 O 2 generated from GOx activity or from other sources .…”