Mild Hyperthermia‐Assisted Coaxial Electrospun Nanofiber Patches for Epicutaneous Allergen‐Specific Immunotherapy

Abstract Epicutaneous immunotherapy (EPIT) is effective and safe to induce sustained protection against anaphylaxis with small doses of allergens. To penetrate the barrier of the stratum corneum, a coaxial nanofiber patch is designed that incorporates natural phase‐change materials (PCM) for mild hyperthermia‐assisted skin permeability, while minimizing the risk of systemic events during immunotherapy. For adaptive immune activation, Toll‐like receptor 7/8 ligand of resiquimod (R848) is combined with ovalbumin (OVA) allergen, thereby stimulating the Th1 pathway and strengthening therapeutic efficacy. For sequential administration, coaxial electrospinning technology is utilized for multiple drug encapsulation and sequential release, where the shell layer consists of poly(vinyl alcohol) (PVA) with OVA dispersion, and the core region is a mixture of PCM and R848. Under mild hyperthermia irritation, the nanofiber patches perform an efficient immunomodulation by manipulating the skin immune system via allergen/adjuvant combinations, which inhibits the secretion of OVA‐specific IgE, and improves lung functions sufficiently in a mouse model of allergic asthma. Mechanistically, the treatment favors IgG2a expression from a Th1‐biased immune response and induces protective regulatory immunity against allergen exposure. Overall, the simplicity and potency of mild hyperthermia mediated EPIT qualifies as a translational strategy for IgE‐mediated allergies with long‐lasting curative effects.