Synthesis of polymer macrogels with rapid and significant response to glucose concentration changes

Abstract

Polymer macrogels that can undergo rapid and significant volume changes in response to an external stimulus, such as a fluctuation in blood glucose concentration, are critical for their versatility. We report here such a polymer macrogel, which is made of a highly-ordered array of poly(phenylboronic acid) microgels tethered chemically to bridging polymers (a thin hydrogel matrix). This unique microstructure makes the newly developed macrogels exhibit a rapid response rate and extraordinarily large responsive swelling ratio upon adding glucose into the bathing medium over a glucose concentration range of 0–30 mM at a physiological pH of 7.4. While the macrogels can swell (e.g., the weight of the macrogels increases by ca. 310-fold if the glucose concentration in the bathing medium increases from 0 to 30.0 mM) and reach stability shortly (reach ∼99% of the maximum change within 90 s) after increasing glucose concentration from 0 to a concentration in the 150.0 μM to 30.0 mM range, the volume changes of the macrogels can be fully reversible within the experimental error even after twenty cycles of adding/removing glucose. The macrogels in this extremely expanded state were somewhat flowable, allowing their use as injectable glucose-sensing materials. With the macrogels as carriers, in vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations, and in vivo studies revealed that these formulations may improve glucose control in streptozotocin-induced diabetic mice subcutaneously administered with the insulin-loaded macrogels.