(718a) Multi-Membrane Systems for Controlled Release

Solutes are often most efficiently deployed in discrete pulses, for example in the delivery of herbicides or drugs. Manual application of each pulse can be labor-intensive, automated application of each pulse can be capital intensive, and both are often costly and impractical. Materials-based approaches such as microcapsules which rupture after a fixed time are limited to 2 or 3 pulses, due to the independent variability in the timing of each pulse. By combining multiple membranes with different functions, however, many pulses can be automatically delivered from a single polymer laminate. Each dose is sequestered in its own stimuli-sensitive depot membrane, which only releases the solute upon contact by the stimulant. The delay between pulses is supplied by reactive barrier membranes, each containing a sacrificial stimulant scavenger. Stacking the two types of membranes alternately and exposing the top of the stack to a constant stimulant, these membranes will release pulses of drug at preset intervals.

We have demonstrated several such systems using acid-sensitive poly(methyl methacrylate-co-dimethylaminoethyl methacrylate) hydrogel membrane to release water-soluble solutes at low pH. Zinc oxide (ZnO) nanoparticles dispersed in a poly(vinyl alcohol) matrix form the barrier membrane, delaying acid permeation for a preset time proportional to the ZnO loading and the square of the membrane thickness, allowing easy tuning of the delay intervals over a wide time scale. Harnessing the swelling pressure of the acid-sensitive hydrogel, each barrier/depot bilayer can delaminate upon solute release, directly exposing the next bilayer to the stimulant source. Controlled release of up to 10 pulses, with variable timing and different solutes in each pulse have been demonstrated. For non-delaminating systems, spent bilayers impede stimulant diffusion to the inner layers and solute diffusion from the inner layers, increasing the delay time and the pulse width. We have constructed a computational model to predict these changes. We have also incorporated catalysts into the barrier membrane to generate stimulant in situ from external pro-stimulants.  For instance, glucose has been converted to organic acid to trigger solute release from the depot. The computational model also guides strategies for positioning the catalyst to minimize the fraction of acid diffusing away from the depot. Both experimental and computational results for these multi-membrane controlled release systems will be discussed.