Enzymatically\nTriggered Drug Release from Microgels\nControlled by Glucose Concentration

This study aims to design microgels for controlled drug\nrelease\nvia enzymatically generated pH changes in the presence of glucose.\nModern medicine is focused on developing smart delivery systems with\ncontrolled release capabilities. In response to this demand, we present\nthe synthesis, characterization, and enzymatically triggered drug\nrelease behavior of microgels based on poly(acrylic acid) modified\nwith glucose oxidase (GOx) (p(AA-BIS)-GOx). TEM images revealed that\nthe sizes of air-dried p(AA-BIS)-GOx microgels were approximately\n130 nm. DLS measurements showed glucose-triggered microgel size changes\nupon glucose addition, which depended on buffer concentration. Enzymatically\ntriggered drug release experiments using doxorubicin-loaded microgels\nwith immobilized GOx demonstrated that drug release is strongly dependent\non glucose and buffer concentration. The highest differences in release\ntriggered by 5 and 25 mM glucose were observed in HEPES buffer at\nconcentrations of 3 and 9 mM. Under these conditions, 80 and 52% of\nDOX were released with 25 mM glucose, while 47 and 28% of DOX were\nreleased with 5 mM glucose. The interstitial glucose concentration\nin a tumor ranges from ∼15 to 50 mM. Normal fasting blood glucose\nlevels are about 5.5 mM, and postprandial (2 h after a meal) glucose\nlevels should be less than 7.8 mM. The obtained results highlight\nthe microgel’s potential for drug delivery using the enhanced\npermeability and retention (EPR) effect, where drug release is controlled\nby enzymatically generated pH changes in response to elevated glucose\nconcentrations.