Composite drug delivery system combining choline-oleic ionic liquid nanomicelles containing quercetin and methyl eugenol with a poloxamer thermosensitive gel for the management of allergic rhinitis

Objective To prepare choline-oleate ionic liquid ([Ch][Ole]IL) nanomicelles co-loading quercetin (QUE) and methyl eugenol (ME) (QUE/ME-NM) and a Poloxamer thermosensitive gel composite delivery system (QUE/ME-NM-TSG) for treatment of allergic rhinitis (AR). Methods QUE/ME-NM were prepared by thin-film hydration combined with a Box–Behnken response surface design and characterized for physicochemical properties and in vitro release behavior. Poloxamer thermosensitive gel was optimized using gelation temperature as the index, and QUE/ME-NM-TSG was constructed by the cold method. Gelation characteristics, rheology, in vitro release and ex vivo nasal mucosal permeation were evaluated. Therapeutic efficacy in an ovalbumin (OVA)-induced AR rat model was assessed by measuring serum inflammatory cytokines, together with nasal mucosal histopathology and apoptosis analyses. Results In QUE/ME-NM, cumulative release of QUE and ME at 30 min were 18.36% and 14.22%, respectively, indicating favorable sustained-release behavior. QUE/ME-NM-TSG underwent rapid gelation at 32 °C within 37 s; drug release conformed to a gel-matrix erosion mechanism (R² = 0.9952). Steady-state permeation rates of QUE and ME through nasal mucosa were 15.97 and 14.79 μg·cm⁻²·h⁻¹, respectively. Nasal imaging demonstrated a residence time of QUE/ME-NM-TSG exceeding 150 min. Moreover, QUE/ME-NM-TSG significantly reduced serum IL-4, IL-5, IL-13 and OVA-specific IgE levels in AR rats, ameliorated nasal mucosal histopathological damage, and decreased apoptosis. Conclusion The QUE/ME-NM-TSG composite delivery system was successfully developed, effectively enhancing nasal delivery efficiency and local retention of hydrophobic drugs and alleviating AR symptoms, and represents a promising nasal administration strategy for allergic rhinitis.