Transdermal Allergen-Specific Immunotherapy Using a Biodegradable Microneedle Array Patch in a Murine Model of Peanut Anaphylaxis

Abstract

Purpose: Peanut anaphylaxis is a widespread challenge, particularly in children. We aimed to confirm the therapeutic effects of transdermal immunotherapy (TDIT) in a murine model of peanut anaphylaxis. Methods: We developed a biodegradable microneedle array patch (MAP) by incorporating peanut extract (PE) with hyaluronic acid. The allergenicity of the PE in MAP was assayed by enzyme-linked immunosorbent assay inhibition. The peanut anaphylaxis model was made with BALB/c or C3H/Hej mouse strains. We measured anaphylaxis clinical scores, as well as the levels of mouse mast cell protease-1 (MCPT-1), PE-specific immunoglobulin E (sIgE), specific immunoglobulin G (sIgG)1, and sIgG2a in serum. T cell populations in the spleen and jejunum were examined using immunohistochemical stains with confocal microscopy. Histological analysis of the jejunum was performed. The production of T helper cell type 2 (Th2) and regulatory T cell (Treg) cytokines by stimulated splenocytes were also measured. Results: The inhibitory capacity of the PE in MAP for PE sIgE was comparable to that of native PE. TDIT with 10 mu g of PE-MAP recovered anaphylaxis score, sIgE, and the MCPT-1 levels, and enhanced sIgG1 and sIgG4 in serum. TDIT also reduced the recruitment of Th2 cells while increasing Treg and Th1 cells in both the spleen and jejunum. However, the efficacy of applying 10 mu g of PE-MAP TDIT twice a week was more pronounced than applying once a week. Additionally, TDIT led to reduced production of Th2 cytokines (interleukin [IL]-4, IL-5, IL-13) and increased production of transforming growth factor-beta by stimulated splenocytes. TDIT attenuated inflammation, mast cell infiltration, and villous damage in the jejunum. Conclusions: PE-MAP TDIT demonstrated therapeutic effects in peanut anaphylaxis, suggesting its potential for developing a novel TDIT for patients with peanut anaphylaxis.