Development of intranasal nanovehicles of itraconazole and their immunological activities for the therapy of rhinovirus infection

• Itraconazole (ITZ)-loaded intranasal (IN) microemulsion (ME) system was developed.
• Its immunological activities for the therapy of rhinovirus infection were assessed.
• The solubility of ITZ in ME was significantly improved compared to that in water.
• Drug release from ME group was enhanced compared to that from suspension group.
• ITZ ME group exhibited lower inflammatory levels than ITZ suspension group in mice.

Itraconazole (ITZ)-loaded microemulsion (ME) systems for intranasal (IN) delivery were developed for the treatment of human rhinovirus serotype 1B (HRV1B) infection. ITZ was incorporated into the oil-in-water (o/w) ME formulation composed of benzyl alcohol (oil), Cremophor EL (surfactant), Solutol HS15 (cosurfactant), and water. The optimized composition of ME was determined by constructing pseudo-ternary phase diagram. ITZ ME formulation with about 150 nm mean diameter and spherical shape was prepared and the solubility of ITZ in blank ME was markedly improved (up to 13.9 mg/mL). The initial value of droplet size was maintained with four times dilution in the aqueous buffer and 72 h incubation. Released amounts of drug from ME formulation were significantly enhanced compared to drug suspension group (p < 0.05). Particularly, ITZ ME group displayed lower levels of inflammatory markers in the lung compared to ITZ suspension group after their IN administration in the HRV1B-infected mouse model (p < 0.05). Developed ITZ ME formulation via IN route can be a promising candidate for the treatment of rhinovirus infection.

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