Gauri P. Misra

New mode of drug delivery: long term autonomous rhythmic hormone release across a hydrogel membrane

This note demonstrates a novel mode of rhythmic drug delivery, which is independent of external modulation or physiological stimulation. Rhythmic behavior is attributed to negative, nonlinear feedback between the swelling state of a hydrogel membrane and the enzymatic conversion of glucose to hydrogen ion. The system pulsates in the presence of a constant level of glucose, thus distinguishing it from insulin delivery devices that respond to changes in glucose concentration. As an example, gonadotropin-releasing hormone (GnRH) was released in short, repetitive pulses over 1 week.

Multipulse drug permeation across a membrane driven by a chemical pH-oscillator

Chemical pH-oscillators provide a potential means for modulating the delivery of acidic or basic drugs across lipophilic membranes. Previous attempts to exploit this notion were not completely successful due to quenching of the pH oscillator in the presence of the drug, most likely by a buffering mechanism. Here we show that multiple, periodic pulses of drug flux across a membrane can be achieved when the concentration of drug is sufficiently low. Advantage is taken of a pH oscillator system whose periodicity is slower than that of previously considered oscillators.