High-yield fabrication of monodisperse multilayer nanofibrous microparticles for advanced oral drug delivery applications

Recent advances in the use of nano- and microparticles in drug delivery, cell therapy, and tissue engineering have led to increasing attention towards nanostructured microparticulate formulations for maximum benefit from both nano- and micron sized features. Scalable manufacturing of monodisperse nanostructured microparticles with tunable size, shape, content, and release rate remains a big challenge. Current technology, mainly comprises complex multi-step chemical procedures with limited control over these aspects. Here, we demonstrate a novel technique for high-yield fabrication of monodisperse monolayer and multilayer nanofibrous microparticles (MoNami and MuNaMi respectively). The fabrication procedure includes sequential electrospinning followed by micro-cutting at room temperature and transfer of particles for collection. The big advantage of the introduced technique is the potential to apply several polymer-drug combinations forming multilayer microparticles enjoying extracellular matrix (ECM)-mimicking architecture with tunable release profile. We demonstrate the fabrication and study the factors affecting the final three-dimensional structure. A model drug is encapsulated into a three-layer sheet (PLGA-pullulan-PLGA), and we demonstrate how the release profile changes from burst to sustain by simply cutting particles out of the electrospun sheet. We believe our fabrication method offers a unique and facile platform for realizing advanced microparticles for oral drug delivery applications.