Glucose-driven chemo-mechanical autonomous drug-release system with multi-enzymatic amplification toward feedback control of blood glucose in diabetes

A second-generation novel chemo-mechanical autonomous drug release system, incorporating various improvements over our first-generation system, was fabricated and evaluated. Enhanced oxygen uptake by the enzyme membrane of the organic engine was facilitated by optimizing the quantity of enzyme immobilizer, PVA-SbQ, and by hydrophobizing the membrane surface. Various quantities of PVA-SbQ were evaluated in the organic engine by measuring the decompression rate, with 1.5mg/cm² yielding optimum results. When fluororesin was used as a hydrophobizing coating, the time to reach the peak decompression rate was shortened 2.3-fold. The optimized elements of the system were evaluated as a unit, first in an open loop and then in a closed loop setting, using a mixture of glucose solution (25mmol/L), ATP and MgCI₂ with glucose hexokinase enzyme (HK) as a glucose reducer. In conclusion, feedback-control of physiologically relevant glucose concentration was demonstrated by the second-generation drug release system without any requirement for external energy.