Smarter glucose-sensitivity of polymeric micelles formed from phenylborate ester-co-pyrenylboronic ester for insulin delivery at physiological pH

Abstract

Exploring an intelligent system capable of releasing insulin in response to glucose level changes would improve the therapeutic potential in diabetes. Herein, we developed a dispersing glucose-responsive group strategy to effectively enhance glucose-sensitivity of the system for the self-regulated delivery of insulin in response to physiological need. One kind of amphiphilic block polymer, which was named poly(ethylene glycol)-block-poly[(2-phenyl boronic esters-1,3-dioxane-5-ethyl) methylacrylate-co-(2-pyrenyl boronic esters-1,3-dioxane-5-ethyl) methylacrylate] MPEG-b-P(PBDEMA-co-PyBDEMA), was fabricated by one-step atom transfer radical polymerization (ATRP) of two monomers PBDEMA and PyBDEMA with MPEG5000-Br as a macroinitiator. These amphiphilic polymers MPEG-b-P(PBDEMA-co-PyBDEMA) were self-assembled to form polymeric micelles with a hydrophobic core composed of both glucose-responsive PPBDEMA and strongly hydrophobic PPyBDEMA. As a result, these polymeric micelles exhibited very slow insulin release at glucose concentration of 1.0 mg mL⁻¹ (normoglycemia) and relatively rapid release behavior at 3.0 mg mL⁻¹ (hyperglycemia) at pH 7.4. Moreover, the glucose-triggered on-off release of insulin was further investigated at pH 7.4 with alternate 1.0 and 3.0 mg mL⁻¹ glucose incubation to exhibit an effective self-regulated insulin delivery in response to physiological glucose level fluctuation. In addition, the encapsulation efficiency (EE) and loading capacity (LC) of insulin were distinctly enhanced to nearly 65% and 20%, respectively. This type of nanocarrier may be a promising candidate for in vivo insulin delivery.