# One-Pot Synthesis of Phenylboronic Acid-Based Microgels for Tunable Gate of Glucose-Responsive Insulin Release at Physiological pH

## TL;DR

This paper introduces microgels that release insulin in response to glucose levels, offering a potential solution for safer diabetes management.

## Contribution

A one-pot synthesis method for glucose-sensitive microgels with tunable insulin release at physiological pH is presented.

## Key findings

- The microgels effectively retain insulin at low glucose levels and release it at high glucose levels.
- The addition of MEO5MA tunes the glucose response to physiologically relevant ranges.
- The microgels show no cytotoxicity in vitro.

## Abstract

Glucose-responsive insulin delivery systems that effectively regulate insulin retention and release in response to real-time fluctuation of glucose levels are highly desirable for diabetes care with minimized risk of hypoglycemia. Herein, we report a class of glucose-sensitive copolymer microgels, prepared from a simple one-pot precipitation copolymerization of 4-vinylphenylboronic acid (VPBA), 2-(dimethylamino) ethyl acrylate (DMAEA), and oligo(ethylene glycol) methyl ether methacrylate (Mw = 300, MEO5MA), for gated glucose-responsive insulin release within the physiologically desirable glucose level range. The composition of the p(VPBA-DMAEA-MEO5MA) copolymer microgels were analyzed using NMR and FTIR spectra. The cis-diols of glucose can reversibly bind with the −B(OH)2 groups of the VPBA component in the microgels, resulting in the formation of negatively charged boronate esters that induce the volume phase transition of the microgels. The DMAEA component is incorporated to reduce the pKa of VPBA, thus improving the glucose sensitivity of the microgels at physiological pH. The neutral hydrophilic MEO5MA component is used to tune the onset of the glucose responsiveness of the microgels to the physiologically desirable levels. The more the MEO5MA component copolymerized in the microgels, the greater the glucose concentration required to initiate the swelling of the microgels to trigger the release of insulin. When the onset of the glucose response was tuned to 4−5 mM, the copolymer microgels retained insulin effectively in the hypo-/normo-glycemic range but also released insulin efficiently in response to the elevation of glucose levels in the hyperglycemic range, which is essential for diabetes management. The copolymer microgels display no cytotoxicity in vitro.