Synthesis of hydrogel-bearing phenylboronic acid moieties and their applications in glucose sensing and insulin delivery

Abstract

In past few years, phenylboronic acids (PBAs) have attracted researcher's attention due to their unique responsiveness towards diol-containing molecules such as glucose.

Stimuli‐Responsive Nanocomposite Hydrogels for Biomedical Applications

“…Inspired by the bioresponsive pancreatic system, advanced biomaterial platforms have been emerging in the form of glucose‐responsive nanocomposite hydrogels, which can be designed by incorporating glucose‐sensitive native proteins (i.e., glucose oxidase enzyme or concanavalin A) or synthetic moieties capable of responding to the presence of glucose and its derivatives (i.e., phenylboronic acid), by dynamically binding to cis‐diol motifs. [ 45,100 ] In this context, several hybrid platforms have been successfully designed with glucose‐responsive insulin delivery features. [ 45,101 ] So far, most hybrid systems are designed to rely on enzyme‐dependent glucose recognition, taking advantage of glucose oxidase conversion of an initial glucose input into two distinct stimuli outputs in the form of decreased pH (i.e., gluconic acid formation) and ROS production (i.e., hydrogen peroxide generation).…”

Recent Applications of Point-of-Care Devices for Glucose Detection on the Basis of Stimuli-Responsive Volume Phase Transition of Hydrogel

“…[93]) less increment in osmotic pressure and resulting in shrinking [8]. For the latter, the binding of PBA to glucose in 1:1 promotes the formation of boronate anion, increasing the mixing free energy and osmotic pressure due to the increased hydrophilic species in hydrogel network, thus swelling [65]. Secondly, Con A (Fig.…”

“…In aqueous solutions, PBA molecule exists in dynamic equilibrium between two forms: trigonal (or planar, uncharged and hydrophobic) and tetragonal form (charged and hydrophilic), can bind 1,2-or 1,3-cis-diols like glucose through the condensation reaction between the added diols and the neutral or charged form of PBA, forming the less stable neutral boronic esters which would rapidly change to neutral boronic acid or charged boronate esters due to the high ring strain on the atom, or stable charged boronate esters accompanied by increased the number of charged species, respectively [56,64,65], as shown in Fig. 4a.…”

“…c Illustration of the GGBP sensitive mechanism with (light gray) or without (dark gray) bound glucose (gray) (reprinted with permission from Ref. [61]) lowering pKa of PBA; when pH < the pKa, the complexation will dissociate due to the boronate anions changing to the trigonal form, and this combination is far stronger than acyclic diols like ethylene glycol and trans-diols [57,65].…”

“…4d) [71]; or covalently immobilizing the aliphatic domain on the benzene ring to promote the hydrophobic effect and enhance affinity to glucose [86]. The other is based on the diboronic acid (multivalency) that two BA moieties could selectively bind one glucose by two-point binding interactions (fructose in the ratio of 1:1) to improve the binding affinity [65,89]. In addition, similar to the 2:1 binding strategy, by exploiting the spatial effect from microspheres, obtain the stronger binding affinity [90].…”