Dissolving microneedle-based epicutaneous immunotherapy for peanut allergy using hyaluronic acid via a film-gluing...

Peanut allergies are life-threatening conditions affecting millions of individuals globally, with severe allergic reactions, such as anaphylaxis, posing significant health risks. Despite advances in allergy treatment, an urgent need remains for safer and more effective therapeutic options that induce long-term immune tolerance while minimizing adverse effects. In this study, we developed a tip-loaded dissolving microneedle (DMN)-based immunotherapy (MIT) system using hyaluronic acid (HA) via a film-gluing method, exploiting HA's intrinsic polysaccharide properties-including biocompatibility, biodegradability, and hydration capacity-to achieve precise and efficient epicutaneous delivery. The DMNs were applied to peanut allergen-sensitized mice, and allergic response was assessed through key indicators including histamine suppression and immunoglobulin E (IgE) and IgG1 levels. Our results demonstrated that MIT induced a more immune tolerance compared to oral immunotherapy (OIT), as evidenced by significantly higher peanut extract (PE)-specific IgG1 and lower PE-specific IgE production. Histamine expression levels were correspondingly lower, indicating a reduced allergic response, and cytokine and chemokine profiling suggested a shift in the immune response from Th2 to Th1, thus supporting enhanced immune tolerance through epicutaneous delivery. Our findings suggest that localized, small-dose allergen delivery using MIT may offer a promising platform for allergy immunotherapy, with broader applications for other allergenic conditions.