Integrated fiber microneedles for oral mucosal vaccine delivery

Thesis (Ph.D.)--University of Washington, 2021The oral mucosa is a promising site for mucosal vaccination because it is easily accessible and contains a rich population of immune cells. However, the current understanding of how vaccine formulation and delivery factors affect the resulting immune response is limited in part by a lack of delivery systems capable of addressing the physical and immunological barriers of the oral mucosa. Several recent studies with immunogen coated solid microneedles have demonstrated that microneedles effectively overcome the physical barriers in the oral mucosa for efficient vaccine delivery. The basic immunogenicity demonstrated in these studies motivates continued exploration of multifunctional microneedle designs capable of incorporating diverse immunogens, controlling release kinetics, and targeting specific immune cell populations in the oral mucosa. As a step toward this ultimate goal, we developed dissolving microneedles containing polymeric nanofibers. We designed an in situ method of nanofiber-microneedle integration that is compatible with a range of relevant microneedle dimensions and preserves the fiber microarchitecture. We demonstrated that nanofibers fabricated from different polymers and encapsulating different pharmaceutical agents are effectively integrated. Finally, we characterized the immunogenicity of integrated fiber microneedles with varying length and release kinetics in the oral mucosa using a model protein antigen. These studies establish integrated fiber microneedles as a highly versatile system which could be used as a tool in future studies to optimize oral mucosal vaccines and to better understand oral mucosal immunity