Allergic-Specific Immunotherapy Using Injectable In Situ Crosslinked Hyaluronic Acid Hydrogels Ameliorates Allergic Response in Murine Allergic Rhinitis Model

Purpose: We present a convenient and safe allergen-specific immunotherapy using injectable hyaluronic acid (HA) hydrogel containing house dust mite (HDM) crosslinked via visible- light-induced thiol-ene reaction. Methods: We developed 2 types of HDM-containing HA hydrogels, namely thiolated HA (SH-HA) + methacrylated HA (MA-HA) (Gel-1) and 4-arm poly (ethylene glycol) (PEG)-SH + MA-HA (Gel-2). The immunotherapeutic effect of the hydrogels was tested using a murine model of allergic rhinitis. Sensitized mice received 3 subcutaneous injections of the HDM extract (subcutaneous immunotherapy [SCIT] group) or phosphate buffer saline (negative and positive control) at 2-day intervals. Mice in the HA hydrogel immunotherapy groups received one subcutaneous injection of each HA hydrogel precursor solution that formed hydrogel by transmitting blue light through the skin. All except the negative control received HDM extract intranasally for 5 days. Nasal symptoms, ear swelling, eosinophil count, antibody levels, and histopathology of the nasal mucosa were analyzed. Results: All HDM-containing immunotherapy groups exhibited reduced nasal symptoms, ear swelling, and eosinophil count in nasopharyngeal lavage compared to the positive control group. Eosinophils, mast cells, and goblet cells in the nasal mucosa decreased in all treatment groups compared to the positive control group. The serum levels of HDM-specific immunoglobulin G (IgG)1 increased in all treatment groups; however, IgG2a levels increased only in the SCIT and Gel-2 groups. Interleukin (IL)-4, 13, and 17 decreased in all treatment groups compared to those in the positive control group, whereas IL-10level increased only in the SCIT and Gel-2 groups. SCIT and Gel-2 treatment showed similar capability to induce regulatory T cells. Conclusions: Injectable HA hydrogel containing HDM reduced allergic symptoms and induced tolerance in a murine model of allergic rhinitis.