Coated Porous Microneedles for Effective Intradermal Immunization with Split Influenza Vaccine

Abstract

In order to alleviate the pain associated with subcutaneous injections, microneedles (MNs) are gaining increasing attention as a novel transdermal drug delivery modality. Among them, porous microneedles (pMNs) are particularly suitable for the delivery of drugs and vaccines whose activity is sensitive to the microneedle preparation process. They can carry drugs actively to achieve an effective load and deliver drugs into the skin. In this study, the biocompatible cellulose acetate (CA) microporous MNs with a large pore size of 1.13 μm ± 0.45 and a high porosity of 74.8% ± 2.8% were prepared by using a safe nonsolvent-induced phase separation (NIPS) method. The MN patches prepared after adsorption of appropriate concentrations of split influenza vaccine fully met the dose loading requirements. A biocompatible carboxymethyl cellulose (CMC) solution was used in the pMN coating to strengthen their mechanical properties, with an average maximum stress of 32.89 N, and to act as a medium for the dispersion of an adjuvant in the coating layer. The influenza vaccine adsorbed in the micropore and the adjuvant dispersed in the coating were released intradermally to exert synergistic effects with different release patterns and rates. The coated pMNs induced an efficient immune response in Wistar rats with a hemagglutination inhibition (HI) titer of ≥1024, which was comparable to that of intramuscular injection. The research is organized around the goal of engineering exploration of innovative technologies, suggesting that pMNs have a tantalizing prospect for future applications. It opens up the possibility of eventually obtaining a simple, easy-to-use, and efficient application technology for the prevention of global epidemics like influenza.

Keywords: coating; influenza vaccine; nonsolvent-induced phase separation; porous microneedles.