Aerosol Inhalation Delivery of Triazavirin in Mice: Outlooks for Advanced Therapy Against Novel Viral Infections

Abstract

Under pandemic-caused emergency, evaluation of the potential of existing antiviral drugs for the treatment of COVID-19 is relevant. Triazavirin, an antiviral drug developed in Russia for per-oral administration, is involved in clinical trials against SARS-CoV-2 coronavirus. This virus has affinity to epithelial cells in respiratory tract, so drug delivery directly in lungs may enhance therapeutic effect and reduce side effects for stomach, liver, kidneys. We elaborated ultrasonic method of triazavirin aerosol generation and investigated the inhalation delivery of this drug in mice. Mean particle size and number concentration of aerosol used in inhalation experiments are 560 nm and 4 × 10 5 cm −3 , respectively. Aerosol mass concentration is 1.6 × 10 −4 mg/cm 3 . Inhalation for 20 min in a nose-only chamber resulted in 2 mg/kg body delivered dose and 2.6 μg/mL triazavirin concentration in blood plasma. Elimination rate constant determined in aerosol administration experiments was k e = 0.077 min −1 , which agrees with the value measured after intravenous delivery, but per-oral administration resulted in considerably lower apparent elimination rate constant of pseudo-first order, probably due to non-linear dependence of absorption rate on triazavirin concentration in gastrointestinal tract. The bioavailability of triazavirin aerosol is found to be 85%, which is about four times higher than for per-oral administration.

Drug Repositioning with GraphSAGE and Clustering Constraints Based on Drug and Disease Networks

“…Excitingly, seven of them have been reported by medical researchers, such as, triazavirin is a guanine nucleotide analog antiviral that has shown efficacy against influenza A and B, including the H5N1 strain. Given the similarities between SARS-CoV-2 and H5N1, health scientists are investigating triazavirin as an option to combat COVID-19 ( Shahab and Sheikhi, 2021 ) ( Valiulin et al, 2021 ). Aspergillus-producing diseases range from allergic syndromes to chronic lung disease and invasive infections and are frequently observed following COVID-19 infection.…”

Inhaled therapy for COVID-19: Considerations of drugs, formulations and devices

“…Valiulin et al ( Valiulin et al, 2021 ) developed the orally available antiviral agent triazavirin in inhaled form and performed the in vivo study on Outbred male mice in an inhalation chamber. The triazavirin aerosol was generated by an ultrasonic nebulizer and the aerosol flowrate in the chamber was maintained at 2.5 L/min by the chamber set-up system.…”

Treatment of respiratory viral infections through inhalation therapeutics: Challenges and opportunities

“…It is in the clinical development phase against SARS-CoV-2 coronavirus. An animal study of triazavirin aerosol inhalation in mice showed 85% bioavailability that is nearly four times higher than that for the traditional per-oral delivery [ 118 ]. The use of intranasal liposomal poly ICLC has been explored for prophylaxis, and treatment as well as a vaccine adjuvant against the highly pathogenic avian influenza A/H5N1 virus [ 119 , 120 ].…”