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

Biosens Bioelectron. 2015 May 15:67:315-20. doi: 10.1016/j.bios.2014.08.044. Epub 2014 Aug 23.

Abstract

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 1.5 mg/cm(2) 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 (25 mmol/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.

Keywords: Artificial pancreas; Chemo-mechanical; Enzyme membrane; Hexokinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques*
  • Blood Glucose
  • Diabetes Mellitus, Type 1 / blood*
  • Drug Delivery Systems*
  • Drug Liberation
  • Enzymes, Immobilized / chemistry
  • Glucose / chemistry
  • Glucose / metabolism*
  • Hexokinase / chemistry
  • Humans
  • Pancreas, Artificial

Substances

  • Blood Glucose
  • Enzymes, Immobilized
  • Hexokinase
  • Glucose