Sublingual dosage form of an antiviral medicinal product based on double-stranded RNA and recombinant interferon alpha-2b: A physicochemical and biological study
Year: 2026
Type: article
Abstract: INTRODUCTION. Sublingual administration of antiviral medicinal products is an alternative method of systemic drug delivery. Interferon (IFN) inducers based on double-stranded RNA (dsRNA), as well as recombinant human IFN preparations, demonstrate a protective effect against a broad spectrum of viruses, including influenza virus and other acute respiratory viral infections. The combined use of IFN and IFN inducers enhances the antiviral efficacy of medicinal products; therefore, the development of a sublingual dosage form of such a medicinal product is a relevant research task. AIM. This study aimed to develop a new sublingual tablet dosage form of a medicinal product based on natural dsRNA isolated from Saccharomyces cerevisiae yeast and recombinant human IFN-α2b. MATERIALS AND METHODS. The sublingual dosage form based on dsRNA and recombinant human IFN-α2b was prepared by direct compression. The structural integrity of dsRNA was assessed by electrophoresis in a 1% agarose gel. The content of IFN-α2b was determined by enzyme-linked immunosorbent assay. The release of the active substances (dsRNA, IFN-α2b) from the sublingual dosage form was assessed by the diffusion method through a semipermeable membrane in a biorelevant medium. The interferon-inducing activity of the preparations was evaluated in outbred male ICR mice; IFN levels in mouse serum were determined by titration in L929 cell culture based on the suppression of the cytopathic effect of murine encephalomyocarditis virus, Columbia strain. RESULTS. The composite preparation in the form of sublingual tablets with the selected excipient composition met the requirements of the General Monograph of the State Pharmacopoeia of the Russian Federation (OFS) for “uniformity of mass” and “uniformity of dosage units”. The presence of the active components, dsRNA and IFN-α2b, in the sublingual dosage form was confirmed. The study of the release of dsRNA and IFN-α2b from the sublingual dosage form into a biorelevant medium showed that complete diffusion was observed within 15 minutes after the start of the study. Preparations containing dsRNA (5 mg) and IFN-α2b (5,000 or 25,000 IU) had more pronounced interferon-inducing activity compared to the dsRNA preparation. Serum IFN titers in mice administered the preparation of the selected composition (5 mg dsRNA and 5,000 IU IFN-α2b) at a dose of 100 μg dsRNA and 100 IU IFN-α2b per mouse were statistically significantly higher than those in the comparison group. CONCLUSIONS. The data obtained indicate that the development of effective antiviral medicinal products based on IFN and its inducer in a sublingual dosage form is promising. Further studies are planned to confirm the antiviral activity of the active components in a cell culture sensitive to human IFN-α using the method described in the State Pharmacopoeia of the Russian Federation (14th edition, OFS.1.7.2.0002.15), as well as in an experimental model of viral infection.
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7222969399