Application of Microneedles to Skin Induces Activation of Epidermal Langerhans Cells and Dermal Dendritic Cells in Mice

Abstract

An adequate immune response to percutaneous vaccine application is generated by delivery of sufficient amounts of antigen to skin and by administration of toxin adjuvants or invasive skin abrasion that leads to an adjuvant effect. Microneedles penetrate the stratum corneum, the outermost layer of the skin, and enable direct delivery of vaccines from the surface into the skin, where immunocompetent dendritic cells are densely distributed. However, whether the application of microneedles to the skin activates antigen-presenting cells (APCs) has not been demonstrated. Here we aimed to demonstrate that microneedles may act as a potent physical adjuvant for successful transcutaneous immunization (TCI). We prepared samples of isolated epidermal and dermal cells and analyzed the expression of major histocompatibility complex (MHC) class II and costimulatory molecules on Langerhans or dermal dendritic cells in the prepared samples using flow cytometry. The expression of MHC class II and costimulatory molecules demonstrated an upward trend in APCs in the skin after the application of 500-and 300-µm microneedles. In addition, in the epidermal cells, application of microneedles induced more effective activation of Langerhans cells than did an invasive tapestripping (positive control). In conclusion, the use of microneedles is likely to have a positive effect not only as an antigen delivery system but also as a physical technique inducing an adjuvant-like effect for TCI.

In Vivo Study on Site of Action of Sinapine Thiocyanate following Acupoint Herbal Patching

“…To date, the mechanisms behind this therapy remain undefined; several studies have indicated that AHP took part in the immunological regulation when treating allergic rhinitis and asthma [ 14 , 15 ]. With an increasing understanding of the skin as an immune system, the intradermal route has emerged as an ideal route to administer vaccines and immunomodulators [ 16 ]. Strong associations were observed between skin reactions and therapeutic efficacy by researchers [ 17 , 18 ].…”

Microneedle systems for delivering nucleic acid drugs

“…Prow et al ( 2010 ) have visualized MN-induced migration of thousands of antigen presenting cells (APCs) in epidermal area of mice after activating with a conventional antigen or DNA vaccine through MN application (Prow et al 2010 ). In addition to serving as a delivery system, MN system may serve as a physical adjuvant by increasing cell death-induced immunity during application (Depelsenaire et al 2014 ; Takeuchi et al 2016 ). Furthermore, because of its benefits of stability and simplicity, using MN is considered as a practical and efficient method for nucleic acid vaccination.…”

Effect of ultrasound treatment of the skin on activation of Langerhans cells and antibody production in rodents

“…In our previous study, we demonstrated that physically stimulating the skin with MNs effectively activated LCs in C57BL/6 mice. [ 5 ] Given that MNs have been used for delivering drugs, including large molecules like antigens, to the skin, drug delivery techniques studied extensively enable effective vaccination to be utilized. [ 2 6 ]…”