Sublingual and buccal allergen delivery: Targeting oral dendritic cells for allergen-specific immunotherapy

Sublingual and buccal routes offer unique advantages for local and systemic drug delivery. Subcutaneous immunotherapy (SCIT) requires repeated injections of allergens and carries a high risk of adverse effects, whereas sublingual immunotherapy (SLIT) offers a safer, noninvasive, needle-free alternative for allergy treatment. However, compared with SCIT, SLIT typically requires 50-100 times higher allergen doses to achieve clinical effectiveness during allergen-specific immunotherapy (AIT), primarily because of the absence of adjuvants or specialized delivery systems. Promoting the availability of aeroallergens and food allergens to oral dendritic cells (DCs) may increase the effectiveness of AIT while reducing the required doses. Such allergen presentation platforms include adjuvants that stimulate Th1 and/or regulatory T-cell responses. Another strategy involves allergen encapsulation or adsorption into nanoparticulates or mucoadhesive systems to increase allergen availability and target oral DCs. This review examines the physiological factors influencing sublingual/buccal allergen delivery, therapeutic mechanisms and clinical development of approved formulations. Furthermore, we categorize and describe natural or synthetic products used as adjuvants or delivery systems that could be considered as candidate allergen presentation platforms for sublingual and buccal administration.