A detachable dissolving microneedles patch as a new effective platform to deliver Japanese encephalitis live attenuated chimeric vaccine

Abstract

The purpose of this study was to develop a detachable dissolving microneedles (dDMNs) patch incorporating Japanese encephalitis live attenuated chimeric vaccine (JE-CV) via skin intradermal (ID) immunization. JE-CV-loaded dDMNs (JE-CV:dDMNs at a mass ratio of 1:4) were successfully formulated from NaHCO3:CS:PVA (sodium bicarbonate:chitosan:polyvinyl alcohol) at 0.25:1:4 mass ratio with 121 needles per patch of 1 cm2. The MN patches showed sufficient mechanical strength to resist compression and maintain their appearance after penetrating excised neonatal porcine skin. After application, the MNs arrays were completely detachable from the backing layer at 1 h (∼91 % of delivery efficiency) as wearing time required, and over 80 % of the needles had dissolved after 2 h. For immune responses, the results found that mice immunized with a half-dose of the JE-CV via ID using a JE-CV-loaded dDMNs patch elicited seroprotection (PRNT50 ≥ 10 titers, recommended by the World Health Organization (WHO)) comparable to mice who received a full dose of the JE-CV via subcutaneous (SC) injection. In contrast, mice immunized with a half-dose of the JE-CV via SC injection did not elicit seroprotection. Mice immunized with a half-dose of the JE-CV-loaded dDMNs via ID stimulated IgA higher than mice immunized with the full-dose ∼1.4 times in saliva and nasal wash. For cytokines’ levels, mice immunized with the full-dose of the JE-CV solution via SC induced interferon-gamma (IFN-ɤ) and interleukin-4 (IL-4), the levels were similar to the half-dose of the JE-CV-loaded dDMNs patch ID immunization (p > 0.05). The results revealed that the JE-CV-loaded dDMNs showed promise for effectively stimulating humoral immune responses (HIR) and cell-mediated immune responses (CMIR) to protect against JEV.