Barrier-Mediated Pulsed Release

While zero-order release has long received most attention from researchers, many therapies require pulsatile release, particularly those with signaling or tolerance issues. While manual pulsatile delivery remains the simplest administration method, automated pulsatile delivery of more than a couple pulses has invariably been complex, requiring an external reservoir of drug which can be precisely pumped through a chronic wound. We are developing a system in which each dose is distributed within a stimuli-sensitive film, protected by a stimuli-scavenging barrier layer. For this generalized system, pH sensitive poly(methyl methacrylate/dimethyl amino ethyl methacrylate) (p(MMA/DMA)) hydrogels are loaded with a model drug (methylene blue) and stacked between layers of poly(vinyl alcohol) (PVA) loaded with zinc oxide nanoparticles. Upon exposure to a general stimulant (in this case, acid) the PVA layers are sequentially exhausted, each allowing a pulse of solute from its underlying hydrogel layer in turn. The timing of these pulses can be varied precisely over a large range, and multiple solutes have been released from a single system.