Safety of applying influenza-antigen-coated microneedles to rat skin and the antigen specific immune response in vivo

Abstract

Purpose Technological advancements and innovations in the use of microneedles for medicinal purposes are constantly emerging. To promote the marketing of microneedles, the safety of microneedle systems during application and storage must be highlighted. Therefore, investigating the toxicity and skin safety of these materials is important. We aimed to determine the physicochemical properties of influenza-antigen-coated microneedle (Influenza MN) and the skin irritation, acute toxicity, and specific antibody production in vivo after applying the coated microneedles to rat skin. Methods We prepared Influenza MN patches using polylactic acid. The protein antigen coating and microneedle morphology were identified using scanning electron microscopy (SEM) and SEM–energy-dispersive X-ray spectroscopy (EDS), and the coating was assayed using a bicinchoninic acid kit. We used the Draize method to assess skin irritation after applying the patches to rat skin and serum biomarkers to assess the systemic toxicity of the patches. We used an enzyme-linked immunosorbent assay to determine the antigen-specific immune response induced by the patches in vivo. Results The antigenic protein coated on the microneedles was visualized by SEM and confirmed by EDS. The protein content of the patches was 96.41 ± 3.18 μg. Treatment with the patches did not cause any significant skin irritation as determined by the Draize method. Applying the patch did not cause systemic toxicity in the rats according to the serum biomarkers but induced a strong antigen-specific immune response in vivo. Conclusion Applying the Influenza MN patches did not cause significant skin irritation or dermal toxicity in rats but induced antigen-specific immune responses in vivo.