pH-Hysteresis of Glucose Permeability in Acid-Doped LCST Hydrogels: A Basis for Pulsatile Oscillatory Drug Release

Some drugs and hormones are efficacious only when delivered in a periodic, pulsatile manner. This observation motivates the construction of periodic pulsatile delivery devices. We report progress towards an implantable device that pulsates autonomously without prompting from an external energy source. The device is conceived by combining understanding of oscillating chemical reactions and of the properties of gels which undergo first-order swelling phase transitions. Chemical oscillators typically include a reaction whose rate law shows hysteresis, coupled to a feedback reaction which causes the system to switch back and forth between branches of the former reaction. First order swelling transitions in hydrophobic acidic gels also feature hysteresis with respect to pH. Coupling swelling hysteresis to transport of the substrate and product of an enzymatic reaction, we predict periodic, pulsatile behavior of the gel/enzyme system. Here we summarize the theoretical basis of the device, demonstrate hysteresis in permeability of a selected membrane, and present initial evidence for oscillatory device behavior.