Delivery of allergen powder for safe and effective epicutaneous immunotherapy

Background: More effective and safer immunotherapies to manage peanut allergy are in great demand despite extensive investigation of sublingual/oral immunotherapy and epicutaneous immunotherapy (EPIT) currently in the clinics. Objective: We sought to develop a powder-laden, dissolvable microneedle array (PLD-MNA) for epidermal delivery of powdered allergens and to evaluate the efficacy of this novel EPIT in peanut-sensitized mice. Methods: PLD-MNA was packaged with a mixture of powdered peanut allergen (PNA), 1,25-dihydroxyvitamin D-3 (VD3), and CpG. Its epidermal delivery and therapeutic efficacy were evaluated alongside PNA-specific forkhead box P3-positive regulatory T cells and IL-10(+) and TGF-beta 1(+) skin-resident macrophages. Results: PLD-MNAwas successfully laden with PNA/VD3/CpG powder and capable of epidermal delivery of most of its content 1 hour after application onto intact mouse skin concomitant with no significant leakage into the circulation or skin irritation. PLD-MNA-mediated EPIT substantially reduced clinical allergy scores to 1 from 3.5 in sham control mice (P <.001) after 6 treatments accompanied by lower levels of PNA-specific IgE and intestinal mucosal mast cells and eosinophils over sham treatments. Moreover, in comparison with allergens administered intradermally, powdered allergens delivered by means of PLD-MNA preferentially attracted immunoregulatory macrophages and stimulated the cells to produce IL-10, TGF-beta, or both at the immunization site, which might account for increased numbers of regulatory T-like cells in lymph tissues in association with systemic tolerance. PNA/VD3/CpG-laden PLD-MNA was safe and required only 6 treatments and one fifth of the PNA adjuvant dose, with improved outcomes when compared with 12 conventional intradermal immunotherapies. Conclusions: PLD-MNA holds great promise as a novel, safe, effective, and self-applicable modality to manage IgE-mediated allergies.