Comparative Study of Two Droplet-Based Dissolving Microneedle Fabrication Methods for Skin Vaccination.

Dissolving microneedles (DMNs) have been widely studied in medical applications due to their pain-free administration, superior efficiency, and safe drug delivery. In skin vaccination, preserving the activity of the encapsulated antigen is an important consideration, as antigen activity is lost during DMN fabrication because of various stress factors. These stress factors vary between fabrication methods and each method affects the antigen's activity to different degrees. In this study, the activity of encapsulated antigens delivered by DMNs is compared between two recently developed DMN fabrication methods; droplet-born air blowing (DAB) and centrifugal lithography (CL) for a model scrub typhus vaccine antigen, ScaA. Although the in vitro analysis of ScaA-loaded DMNs (ScaA-DMNs) does not show any differences in physical properties depending on the fabrication methods, the immunogenicity of the CL-produced ScaA-DMN is significantly higher based on cytokine measurement and humoral immunity. DAB and CL differ in their solidification conditions, suggesting that solidification factors critically affect the encapsulated antigen's activity. ScaA-DMNs may also be stably stored for 4 weeks at room temperature. In conclusion, CL is a superior DMN fabrication method compared with DAB, and this study proves that DMN is feasible and practical for skin vaccination.