Nasal delivery of an immunotherapeutic vaccine in thermosensitive hydrogel against allergic asthma.

Asthma poses a significant threat to public health, with an estimated burden of over 334 million people worldwide. Available treatments are often inadequate. We developed a thermo-sensitive hydrogel vaccine containing allergen and FK506 that induced immune tolerance via intranasal administration to treat experimental allergic asthma. The hydrogel delivery system was formulated based on Poloxamer 407 (P407), Carbopol 974P NF, and Polyoxyl 15 hydroxystearate (Kolliphor HS15, HS15). It flowed freely at room temperature and rapidly formed a hydrogel in the nasal cavity once the temperature rose over 33 °C. Ovalbumin and FK506 were slowly released from the hydrogel form and their mucosal residence time was significantly prolonged compared to the liquid formulation. In both an OVA-induced asthma model and an HDM-induced asthma model, the vaccines formulated in hydrogel gave lower levels of eosinophilic inflammation, and airway remodeling. The reduction of lung function was ameliorated, and Foxp3-expressing CD4 + Treg cells were significantly higher. The frequency of Foxp3 + Tregs in lung-draining lymph nodes (dLNs) was correlated with the amelioration. Depletion of Foxp3 + Treg cells abolished the beneficial effects of the allergen/FK506 hydrogel vaccinations. Thus, the allergen/FK506 hydrogel formulation has the potential to be a delivery system for therapeutic allergy vaccines to induce immune tolerance.