Anti-otomycotic potential of nanoparticles of leaf extract: an integrated , and phase 0 clinical study.

Otomycosis is a serious superficial mycotic infection of the outer ear canal caused by some pathogenic species of and . The infection remains a challenge to clinicians owing to the incomplete efficacy of market-available antifungal agents and high recurrence rates. The leaf ethanol extract showed efficacy against SC5314, compared to Nystatin® as a reference with MIC values of 7 and 718.33 μg ml, respectively. The extract was mixed with lecithin and chitosan to give core/shell giant nanoparticles, with a good zeta potential (+59.2 mV), a suitable entrapment efficiency (61%) and an enhanced release reaching up to 90% at 8 h. Clinical isolates from oomycote patients were identified DNA sequencing as , and , and the effect of the prepared nanoparticles was tested against them disk diffusion assay to give inhibition zones of 75, 55 and 55 mm, compared to Nystatin® with 35, 25 and 20 mm, respectively. Interestingly, patients treated with the -loaded nanoparticles experienced improvement within 1 week with no recurrence for more than 3 months. To have some insight into the bioactive components in the extract, LC-HRMS-based identification has been employed which led to the annotation of 27 compounds. Subsequent comprehensive investigation suggested some alkaloids to be responsible for the activity targeting the fungal 14-α-demethylase enzyme (CYP51B). Our study revealed that extract-loaded nanoparticles attained an enhanced antifungal efficacy compared to Nystatin® and therefore they can be employed against invasive and drug-resistant otomycotic infections.