(171h) Pulsatile Release of Model Drugs Through Layered Polymers

Barrier-Mediated Pulsatile Release (BMPR) systems offer a materials-based alternative for automated pulsatile drug delivery, without pumps, power supplies, or complex circuitry. While earlier materials-based approaches such as delayed-release microcapsules are limited to two or three pulses due to the independent nature of each pulse’s timing control, BMPR systems link the timing of each pulse to the previous pulse. Each dose of drug is sequestered in its own stimuli-sensitive depot, releasing only upon contact with the stimulant. These depots are stacked with sacrificial barriers in between, each of which block the stimulant for a predetermined time. For instance, layers of soluble drug may be separated by degradable polymer layers. Water, as the stimulant, will erode the polymer layer over a fixed period of time, followed by quick dissolution and release of the underlying drug and the start of degradation for the next polymer layer. This example, however, is quickly limited by irregular polymer erosion, a single stimulant (water), and difficulty in scaling delay times. 

In this presentation, we report the development of a generalized BMPR system which overcomes those limitations. Drug (methylene blue) was immobilized in pH-sensitive polymer (poly(methyl methacrylate-co-dimethylaminoethyl methacrylate)) which released only at low pH. Zinc oxide (ZnO) nanoparticles immobilized in a pH-insensitive matrix (poly(vinyl alcohol)) served as the barrier layer. The time required for acid to penetrate the barrier layer scaled with the ZnO concentration and with the square of the polymer thickness, allowing wide scaling of the delay time with only minor changes to the barrier layer. This system has demonstrated tuned release using a citric acid stimulant to produce up to ten pulses of model drug (methylene blue) over various preset timescales. This system has also demonstrated the alternate release of multiple solutes (methylene blue and methyl orange) at a regular time intervals up to five pulses from a single BMPR device. This presentation will discuss the synthesis of depot & barrier films, design of experimental BMPR device, pulse behavior of model drugs and introduce efforts to further generalize this delivery strategy by incorporating glucose as a stimulant.