Hong Kong: A team of researchers has developed an inhalable dry powder formulation of tamibarotene, a repurposed drug, that has shown broad-spectrum antiviral activity in animal models against SARS-CoV-2, MERS-CoV, and influenza A H1N1 virus.
Tamibarotene is currently marketed in Japan as an oral tablet for the treatment of acute promyelocytic leukaemia. However, toxic side effects are expected due to the extensive systemic exposure when a high dose is administered to compensate for insufficient lung distribution.
Pulmonary delivery, on the other hand, is a non-invasive administration route that can maximise local concentration in the lung while reducing systemic exposure, lowering the risk of adverse effects and improving therapeutic efficacy.
Spray freeze drying, a particle engineering technique that combines spray freezing and freeze drying to produce particles with excellent aerosol properties for inhalation, was used by the team led by the University of Hong Kong (HKUMed) to prepare the inhaled dry powder formulation of tamibarotene.
The researchers discovered that an intratracheal dose of tamibarotene powder significantly reduced virus titer and viral RNA load of SARS-CoV-2 in the lungs of hamsters, and that the antiviral efficacy was comparable to that of intratracheally administered remdesivir.
The broad-spectrum anti-coronavirus activity of inhaled tamibarotene powder was also demonstrated as pre-challenge prophylaxis in MERS-CoV-infected mice.
Furthermore, the remarkable anti-influenza activity of tamibarotene powder formulation was demonstrated by improved mouse survival and disease severity when administered intratracheally as prophylaxis or intranasally as treatment.The findings have been published online in Advanced Therapeutics.
“There is currently no antiviral inhaled powder formulation available on the market for COVID-19 treatment. Tamibarotene dry powder with broad-spectrum antiviral activity represents a novel strategy for COVID-19 management, particularly as prophylaxis and treatment for outpatients when in-patient care is unavailable “Jenny Lam, Associate Professor in the Department of Pharmacology and Pharmacy at HKUMed, agreed.
“With tamibarotene’s favourable safety profile and the current study’s findings, clinical trials evaluating inhaled tamibarotene for its safety and as an at-home treatment for COVID-19 could be considered,” Lam said.
According to the researchers, because of the ease of (self-)administration, inhaled powder formulations of broad-spectrum antiviral drugs can be used as prevention and treatment for respiratory viral infections on an outpatient basis.