Nasal absorption of interferon: enhancement by surfactant agents

Abstract

The effect of spraying the nasal mucosa with an aerosol of recombinant human interferon-alpha (IFN-alpha 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-alpha 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-alpha 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.