Enhanced brain penetration of pretomanid by intranasal administration of an oil-in-water nanoemulsion

Abstract

Aim: To enhance the drug delivery to the brain with an oil-in-water nanoemulsion of pretomanid via intranasal (IN) administration. Materials & methods: The study involved 70 male Sprague–Dawley rats (160–180 g) that received either 20 mg/kg body weight (b.w.) a nanoemulsion or a 20 mg/kg b.w. of pretomanid in solution via the IN route. The drug was quantified by liquid chromatography–tandem mass spectrometry to investigate whole tissue–drug concentrations, and mass spectrometric imaging to visualize drug localization in the brain. Results: Nanoemulsion delivery concentrations of pretomanid in the brain reached peak concentrations (Cmax) of 12,062.3 ng/g that is significantly higher than the required therapeutic level. The mass spectrometric imaging analysis clearly showed a time dependent and uniform distribution in the brain. Conclusion: The results of this study show that IN delivery of oil-in-water nanoemulsion may be very promising for targeting anatomical tuberculosis reservoirs, such as the brain.