Enzymatically Triggered Drug Release from Microgels Controlled by Glucose Concentration.

Abstract

This study aims to design microgels for controlled drug release via enzymatically generated pH changes in the presence of glucose. Modern medicine is focused on developing smart delivery systems with controlled release capabilities. In response to this demand, we present the synthesis, characterization, and enzymatically triggered drug release behavior of microgels based on poly(acrylic acid) modified with glucose oxidase (GOx) (p(AA-BIS)-GOx). TEM images revealed that the sizes of air-dried p(AA-BIS)-GOx microgels were approximately 130 nm. DLS measurements showed glucose-triggered microgel size changes upon glucose addition, which depended on buffer concentration. Enzymatically triggered drug release experiments using doxorubicin-loaded microgels with immobilized GOx demonstrated that drug release is strongly dependent on glucose and buffer concentration. The highest differences in release triggered by 5 and 25 mM glucose were observed in HEPES buffer at concentrations of 3 and 9 mM. Under these conditions, 80 and 52% of DOX were released with 25 mM glucose, while 47 and 28% of DOX were released with 5 mM glucose. The interstitial glucose concentration in a tumor ranges from ∼15 to 50 mM. Normal fasting blood glucose levels are about 5.5 mM, and postprandial (2 h after a meal) glucose levels should be less than 7.8 mM. The obtained results highlight the microgel's potential for drug delivery using the enhanced permeability and retention (EPR) effect, where drug release is controlled by enzymatically generated pH changes in response to elevated glucose concentrations.