Fast-dissolving microneedles with tip-loaded ovalbumin for transcutaneous allergen-specific immunotherapy.

Abstract

The popularization of allergen-specific immunotherapy (AIT) is impeded by the frequent administration and extended periods with high risk of adverse reactions. Considering mass antigen-presenting cells in epidermal and dermal regions, we propose a transcutaneous AIT strategy for desensitization and protection against anaphylaxis. Structurally, a hyaluronic acid (HA)-based fast-dissolving microneedle array is prepared by two-step casting method, in which the needle tips are mixed encapsulated with ovalbumin allergen (OVA-MN). The composition of polymer-additive complexes is optimized to balance mechanical performance and disintegration efficiency, thus creating OVA-MN arrays with efficient allergen skin penetration, minimal administration time and frequency. Once inserted into skin, OVA-MN arrays rapidly dissolve and release accurate OVA dose in epidermal and dermal layers, giving rise to the reliable immune-remodeling effects. Compared with the recognized subcutaneous injection, only a total dose of 75 μg over 3 weeks can ameliorate allergen-specific IgE responses, and improve lung functions in a mouse model of allergic asthma, demonstrating the antigen dose- and time-sparing potential of OVA-MN at a safe level. Collectively, OVA-MN arrays described here provide an innovative approach for allergy treatments with convenient administration as well as satisfactory outcomes.