Physicochemical and biologic properties of interferons and their potential uses in drug delivery systems.

Interferons (IFNs) are a complex group of proteins and glycoproteins able to express antiviral, immunomodulatory, and differentiation activities. In physiological conditions, they are produced upon induction, in basal amounts, and in restricted microenvironments where they act in a paracrine fashion, hardly reaching the circulation and not affecting parenchymal cells. In some acute infections, production of IFN is diffused and, therefore, IFN levels become detectable in plasma, and side effects, such as the typical flu-like syndrome, ensue. A similar situation occurs during pharmacological therapy, particularly when IFN is administered through conventional routes (IV, IM, and SC). We have finally realized that IFNs are normally not circulatory proteins, and because they are unselective during therapeutic intervention, toxicity can overcome beneficial effects. For this reason, there is a pressing need to optimize treatment, dosages, and schedules for improving the therapeutic index. A further important issue is the definition of routes of IFN administration able to achieve the maximal activity where needed, and in fact, when IFNs are used as cytostatic drugs, regional therapy improves the treatment. However, when IFNs are used as immunomodulatory agents, other strategies must be sought, and the interaction of IFN with epithelial membranes and mucosal associated lymphoid tissue becomes important. Hence, delivery via oropharyngeal, intestinal, rectal, bronchioalveolar, and lymphatic routes appears useful probably because they simulate the physiological distribution and action of IFNs.