Issue 44, 2024

pH and glucose dual-responsive phenylboronic acid hydrogels for smart insulin delivery

Abstract

Phenylboronic acid (PBA) is a widely exploited glucose-sensitive element for constructing glucose-responsive hydrogels to enable smart insulin delivery. However, its relatively high intrinsic pKa affects its binding with glucose under physiological conditions and thus limits its application. Herein, we developed a series of boronate-containing PLP–PBA polymers by conjugating glucose-sensitive 3-aminophenylboronic acid (3-PBA) onto the backbone of a metabolite-derived, pH-responsive poly-L-lysine isophthalamide (PLP) polymer with a pKa value of 4.4 at various substitution degrees. Dual-responsive LME–(PLP–PBA) hydrogels were further synthesized by crosslinking the PLP–PBA polymers with L-lysine methyl ester (LME). The rheological properties and swelling ratio of the hydrogel could be manipulated by the PBA grafting degree and crosslinking ratio. With the increase of pH and glucose concentration, the pore size of the hydrogel enhanced, thus promoting the release of loaded insulin. Under physiological conditions, the hydrogel with optimal formulation could establish acute pH-responsive and glucose-responsive insulin release. The development of this dual-responsive hydrogel suggests a strategy to overcome the high pKa problem associated with PBA and provide a promising delivery system for smart insulin delivery.

Graphical abstract: pH and glucose dual-responsive phenylboronic acid hydrogels for smart insulin delivery

Supplementary files

Article information

Article type
Paper
Submitted
22 Aug 2024
Accepted
21 Oct 2024
First published
22 Oct 2024

Soft Matter, 2024,20, 8855-8865

pH and glucose dual-responsive phenylboronic acid hydrogels for smart insulin delivery

K. Yang, H. Bo, D. Ma, M. Peng, Q. Liu, Z. Heng, Z. Gu, X. Liu and S. Chen, Soft Matter, 2024, 20, 8855 DOI: 10.1039/D4SM01004C

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