Quaternized chitosan-coated liposomes enable pH-independent nasal mucoadhesion and a sustained local depot for mometasone furoate.

Limited nasal deposition and rapid clearance compromise the effectiveness of intranasal therapy for allergic rhinitis. Quaternized chitosan (QCS), which carries a permanent positive charge at the near-neutral pH of the nasal cavity, overcomes the pH-dependent limitations of conventional chitosan coatings. In this study, quaternized chitosan-modified liposomes encapsulating mometasone furoate (QCS-MF-Lip) were developed to enhance mucoadhesion and establish a local drug depot. The optimized formulation exhibited a small particle size (170 ± 1 nm) with a narrow size distribution (PDI 0.232 ± 0.011). QCS-MF-Lip showed a 5.26-fold higher mucin-binding affinity and approximately 4.7-fold greater ex vivo mucosal retention (19.59 ± 0.62 μg·cm⁻2) compared with unmodified liposomes and the commercial spray Nasonex®, respectively. In a rat model of allergic rhinitis, QCS-MF-Lip significantly alleviated symptoms and demonstrated superior therapeutic efficacy relative to Nasonex®, as reflected by reduced histamine levels and enhanced anti-inflammatory effects. These results suggest that permanently cationic QCS is a promising strategy for pH-independent nasal mucoadhesion and the establishment of a local intranasal drug depot.