On-site loading of powder-attached microneedles enables quantitative and reproducible intradermal vaccine delivery

Abstract

Conventional vaccination relies on liquid formulations that require cold-chain storage and administration by trained healthcare personnel, creating logistical barriers in resource-limited settings. Microneedle-based intradermal delivery enables solid vaccine administration; however, most microneedle vaccines are manufactured as pre-loaded products, limiting on-demand preparation and increasing operational and regulatory complexity. This study presents an on-site loaded powder-attached microneedle platform (On-site P-MNs), in which vaccine-free MNs bearing a silicone adhesive surface and solid OVA powders are supplied separately and combined immediately prior to administration. Lyophilized OVA formulations stabilized with trehalose were prepared, milled, and size-controlled to obtain powders suitable for reproducible attachment. A bead-assisted shaking process enabled practical on-site loading, and a portable air-blow step selectively removed weakly bound powder to improve loading uniformity and mechanical stability. Using identical microneedle geometry and the same powder batch, on-site loading achieved predictable protein content. Ex vivo porcine skin studies confirmed complete insertion and comparable OVA delivery efficiency between pre-loaded and On-site P-MNs. In a mouse immunization study, On-site P-MNs induced antigen-specific IgG responses comparable to those of Pre-loaded PMNs at the same nominal dose. Overall, On-site P-MNs provide a simple, portable strategy for on-demand intradermal delivery of solid vaccine formulations.