Pulmonary and intranasal delivery of thymoquinone-loaded nanoparticles for mucormycosis & covid-19

Abstract

India is currently reporting a massive increase of mucormycosis infection among Covid-19 patients. The opportunistic black fungus infection affects the lungs and the brain. Depending on the infected organs, morbidity and mortality rates are between 50% and 100%. To save patients’ life, it is frequently necessary to remove jaws and eyes. The drug of the first choice for the treatment of mucormycosis in the subcontinent is amphotericin B. There are two problems with amphotericin B: First, it is currently not available in many pharmacies in India, and second, its effect is restricted by its limited passage across the blood-brain barrier. Recently, it was shown that thymol is highly effective against Rhizopus oryzea, the fungus causing 70% of mucormycosis. In contrast to amphotericin B, which in the case of mucormycosis is administered intravenously, thymol can reach the lungs via inhalation and the brain via the nose-to-brain route. Importantly, thymoquinone (TQ) has all the relevant biological properties of thymol and has already been successfully used to treat Covid-19, as demonstrated in clinical studies. In addition to the action spectrum of thymol, TQ can act as a reactive oxygen species and oxidize pathogens upon contact, thereby recommending itself for both treatment of Covid-19 and infections with the black fungus. For maximum efficacy, comprising biodistribution, bioavailability, and drug functionality, we describe innovative strategies based on nanomedicines for targeted delivery of TQ to the lungs and intranasal delivery to the brain, bypassing the blood-brain barrier. After these promising strategies as the next step, a clinical study for proof of concept should be initiated.