Graphical abstract Highlights • Drug at tip detachable microneedles (DDMN) are developed for transdermal immunization of subunit vaccine. • Drug at tip DDMN can deliver drug into dermis with minimal accumulation at stratum corneum. • DDMN has 86% delivery efficiency. • Model antigen OVA embedded in DDMN is stable at least 35 days at room temperature. • At the same dose, DDMN produces 10-fold stronger anti-OVA responses compared to IM vaccination. Although vaccine administration by microneedles has been demonstrated, delivery reliability issues have prevented their implementation. Through an ex vivo porcine skin experiment, we show visual evidence indicating that detachable dissolvable microneedles (DDMN) can deposit cargo into the dermis with insignificant loss of cargo to the stratum corneum. Using ovalbumin (OVA), a model antigen vaccine, as a cargo, the ex vivo experiments yielded a delivery efficiency of 86.08 ± 4.16 %. At room temperature, OVA could be stabilized for up to 35 days in DDMN made from hyaluronic acid and trehalose. The DDMN matrix could improve the denaturation temperature of the OVA from around 70–120 °C to over 150 °C, as demonstrated by differential scanning calorimetric analysis. In vivo delivery of OVA antigen into the mice’s skin via DDMN elicited 10 times higher specific antibody responses compared to conventional intramuscular injection. We envision DDMN as an effective, precise dosing, intradermal vaccine delivery system that may require no cold-chain, offers a dose-sparing effect, and can be administered easily.
【저자키워드】 Subunit vaccine, vaccine stability, Transdermal vaccination, Microneedles,