Advances in the Design of Phenylboronic Acid-Based Glucose-Sensitive Hydrogels

Abstract

Diabetes, characterized by an uncontrolled blood glucose level, is the main cause of blindness, heart attack, stroke, and lower limb amputation. Glucose-sensitive hydrogels able to release hypoglycemic drugs (such as insulin) as a response to the increase of the glucose level are of interest for researchers, considering the large number of diabetes patients in the world (537 million in 2021, reported by the International Diabetes Federation). Considering the current growth, it is estimated that, up to 2045, the number of people with diabetes will increase to 783 million. The present work reviews the recent developments on the hydrogels based on phenylboronic acid and its derivatives, with sensitivity to glucose, which can be suitable candidates for the design of insulin delivery systems. After a brief presentation of the dynamic covalent bonds, the design of glucose-responsive hydrogels, the mechanism by which the hypoglycemic drug release is achieved, and their self-healing capacity are presented and discussed. Finally, the conclusions and the main aspects that should be addressed in future research are shown.

Rheology as a Tool for Fine-Tuning the Properties of Printable Bioinspired Gels

“…The self-healing ability is given by the presence of dynamic reversible bonds in a network which are destroyed when high forces are applied and then reestablished in time. Such reversible bonds could be noncovalent physical bonds (such as hydrogen bonding, hydrophobic, host–guest, electrostatic interactions, π–π stacking, and metal coordination) [ 114 , 115 ] or covalent bonds (such as disulfide or imine bonds, boronic esters, reversible diarylbisbenzo-furanone crosslinking, and urea–urethane exchange) [ 115 , 116 , 117 , 118 , 119 ].…”

Stimuli-Responsive Hydrogels for Protein Delivery

“…There is a dynamic equilibrium between the charged and uncharged forms of PBA in aqueous media. When the ionized form of PBA in insulin-loaded hydrogels binds to glucose, the combined effect of polymer chain repulsion and increased hydrophilicity drives insulin release along with the rapid expansion of the hydrogel [109,110].…”

Rational Design and Development of Polymeric Nanogels as Protein Carriers

“…However, such systems still present limitations in terms of sugar affinity, and need to be carefully designed to provide a selective response to glucose with respect to other sugars (i.e., fructose, mannose). [129] In this regard, Li et al developed a NG system composed of PEG and poly(cyclic phenylboronic ester) using a click chemistry approach. [130] Although the polymers were per se sensitive to glucose and H 2 O 2 , the release of insulin could be enhanced by incorporating glucose oxidase (GOx) that increased the amount of H 2 O 2 in the presence of glucose.…”

“…However, such systems still present limitations in terms of sugar affinity, and need to be carefully designed to provide a selective response to glucose with respect to other sugars (i.e., fructose, mannose). [ 129 ] In this regard, Li et al. developed a NG system composed of PEG and poly(cyclic phenylboronic ester) using a click chemistry approach.…”