Nasal Absorption of Interferon: Enhancement by Surfactant Agents

Abstract

The effect of spraying the nasal mucosa with an aerosol of recombinant human interferon-α (IFN-α_2a) was studied in an animal model, the sheep, because cultures of sheep cells were found to be responsive to the antiviral activity of this IFN. Binding assays with ¹²⁵I-labeled IFN-α_2a detected very few receptors in sheep nasal mucosa, but a membrane fraction prepared from this mucosa had abundant high-affinity receptors. Nasal mucosa homogenates were prepared from the turbinates of sheep that had been sprayed with IFN-α_2a aerosols, and the 2′,5′-oligoadenylate (2-5A) activity induced in response was measured. To try to enhance the permeability of the mucosa, surfactant agents were added to the IFN and aerosols generated. There were measurable levels of 2-5A synthetase after aerosols with added sodium deoxycholate or, better, polyoxyethylene 9-lauryl ether. This latter surfactant was well tolerated in previous studies with intranasally administered insulin. The level of 2-5A synthetase induced was related to the dose of IFN, and the increased activity persisted up to 72 h after an IFN aerosol. These studies suggest that surfactant agents may make IFN aerosols much more effective for the prophylaxis of respiratory virus infections.