Microneedle-Mediated Vaccine Delivery to the Oral Mucosa

The oral mucosa is a minimally invasive and immunologically rich site that is underutilized for vaccination due to physiological and immunological barriers. To develop effective oral mucosal vaccines, key questions regarding vaccine residence time, uptake, adjuvant formulation, dose, and delivery location must be answered. However, currently available dosage forms are insufficient to address all these questions. An ideal oral mucosal vaccine delivery system would improve both residence time and epithelial permeation while enabling efficient delivery of physicochemically diverse vaccine formulations. Microneedles have demonstrated these capabilities for dermal vaccine delivery. Additionally, microneedles enable precise control over delivery properties like depth, uniformity, and dosing, making them an ideal tool to study oral mucosal vaccination. Select studies have demonstrated the feasibility of microneedle-mediated oral mucosal vaccination, but they have only begun to explore the broad functionality of microneedles. This review describes the physiological and immunological challenges related to oral mucosal vaccine delivery and provides specific examples of how microneedles can be used to address these challenges. It summarizes and compares the few existing oral mucosal microneedle vaccine studies and offers a perspective for the future of the field.