A team of researchers has developed an inhalable dry powder formulation of tamibarotene -- a repurposed drug -- which has showed broad-spectrum antiviral activity against SARS-CoV-2, MERS-CoV and influenza A H1N1 virus following pulmonary delivery in animal models.
Tamibarotene is available as an oral tablet for the treatment of acute promyelocytic leukemia currently marketed in Japan. But when a high dose is administered to compensate for the insufficient lung distribution, toxic side effects are expected because of the extensive systemic exposure.
Particle Engineering Technique
By contrast, pulmonary delivery is a non-invasive administration route that can maximise local concentration in the lung and reduce systemic exposure, thereby reducing the risk of adverse effects and improving therapeutic efficacy.
The team, led by the University of Hong Kong (HKUMed), prepared the inhaled dry powder formulation of tamibarotene by spray freeze drying, a particle engineering technique that combines spray freezing and freeze drying to produce particles with excellent aerosol properties for inhalation.
The researchers found that a dose of tamibarotene powder delivered by intratracheal administration significantly reduced virus titer and viral RNA load of SARS-CoV-2 in the hamsters' lungs, and the antiviral efficacy was comparable to intratracheally administered remdesivir.
The broad-spectrum anti-coronavirus activity of inhaled tamibarotene powder was also demonstrated in MERS-CoV-infected mice model as pre-challenge prophylaxis.
Improved Survival Rate of Mice
Moreover, remarkable anti-influenza activity of tamibarotene powder formulation was demonstrated by the improved survival rate of mice and alleviated disease severity when administered either intratracheally as prophylaxis or intranasally as treatment. The findings have been published online in Advanced Therapeutics.
"Currently, there is no inhaled powder formulation of antiviral available on the market for Covid-19 treatment. Tamibarotene dry powder with broad-spectrum antiviral activity presents a new strategy for Covid-19 management, especially as prophylaxis and treatment for outpatients when in-patient healthcare cannot be provided," said Jenny Lam, Associate Professor, Department of Pharmacology and Pharmacy, HKUMed.
"With the favourable safety profile of tamibarotene and based on the findings in the present study, clinical trials evaluating inhaled tamibarotene for its safety and as at-home treatment for Covid-19 could be considered," Lam said.
Inhaled powder formulation of broad-spectrum antiviral drugs can be used on an outpatient basis due to the ease of (self-)administration as prevention and treatment for respiratory viral infections, the researchers said.