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

Authors:
Dr Adeola Shobo, PhD
Dr Adeola Shobo, PhD
McGill University
Dr
Montreal , McGill University | Canada
Annapurna Pamreddy
Annapurna Pamreddy
University of Girona
Spain
Hendrik G Kruger
Hendrik G Kruger
University of KwaZulu-Natal
South Africa
Maya M Makatini
Maya M Makatini
University of KwaZulu-Natal
South Africa
Tricia Naicker
Tricia Naicker
School of Health Sciences
Sooraj Baijnath
Sooraj Baijnath
University of KwaZulu-Natal
South Africa

Nanomedicine (Lond) 2018 05 23;13(9):997-1008. Epub 2018 May 23.

Catalysis & Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.

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 (C) 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.

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http://dx.doi.org/10.2217/nnm-2017-0365DOI Listing
May 2018
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