Glucose-Sensitive Nanoparticles for Controlled Insulin Delivery

Abstract

A novel reverse microemulsion (RM) mediated synthesis of glucose-responsive nanoparticles was developed for controlled insulin delivery. Nanoparticles were constructed using a model system comprised of dextran, poly(α-1,6 glucose), physically crosslinked with the tetrafunctional glucose-binding protein, Con A. A rapid-screening technique was used to quantify RM phase behavior in the presence of dextran, Con A and insulin. The extent of the RM existence region diminishes with increasing dextran and Con A concentrations and with increasing dextran molecular weight. Crosslinking efficiency between Con A and fluorescein isothiocyanate dextran (FITC-Dex) was found to depend on the total concentration of Con A as well as the ratio of Con A to FITC-Dex. Functionalizing dextran with higher affinity mannose ligands and increasing dextran molecular weight both improved crosslinking efficiency. The nanoparticles dissolved when dispersed in buffered saline solutions containing elevated glucose concentrations and were most responsive within the physiological range. Finally, insulin was encapsulated in select formulations and found to release preferentially at these elevated glucose concentrations.