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.