Intranasal delivery of levocetirizine via transethosomal thermosensitive in situ gel: A promising strategy for enhanced nasal absorption and antihistamine action in allergic rhinitis

Allergic rhinitis has shown a rising prevalence throughout the years, necessitating the implementation of more effective and safe treatment strategies. Levocetirizine (LVC) is an antihistamine of the second generation used for Allergic Rhinitis, Allergic Conjunctivitis, atopic and contact dermatitis, eczema, and urticaria. This study proposed a transethosomal thermosensitive in-situ gel as an intranasal delivery system experimentally for the first time to treat AR in animal models. LVC-loaded transethosomes (LVC-TEs) were prepared using the thin film hydration method. The zeta potential, particle size, polydispersity index, and entrapment efficiency (EE %) were then evaluated. Additionally, TEM and FTIR investigations were performed on the optimized LVC-TE formulation (TE1). The optimized formula integrates into a thermosensitive in-situ gel based on poloxamer 407 and 188, and hydroxypropyl methylcellulose as a mucoadhesive polymer (TE1-ISG). The evaluation of TE1-ISG involved assessing various parameters, and ex-vivo permeation. TE1 displayed smooth spherical nanoparticles with the highest EE% (92.58 ± 1.21), optimum particle size (130.64 ± 2.10 nm), polydispersity index (0.46 ± 0.04), and zeta potential (19.52 ± 0.52 mV). The release profile of TE1 displayed an initial burst followed by sustained release within 24 h. AR was experimentally induced in 24 rats through ovalbumin sensitization followed by nasal challenges. Serum levels of IgE, histamine, PAF, IL-1β, and IL-5 were measured using ELISA, along with PAF and LTB4 levels in the nasal mucosa. The expression of PGD2 and CCL24 mRNA was analyzed via qRT-PCR. Histopathological and immunohistochemical evaluations were performed to assess TGF-β and FOXO1 expression. This study demonstrates that the developed intranasal TE1-ISG provides an effective delivery platform, showing positive pharmacodynamics effects in treating OVA-induced rhinitis in rats, and represents a novel and promising strategy for AR treatment.