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Journal Article
Research Support, Non-U.S. Gov't
Enhanced brain penetration of pretomanid by intranasal administration of an oil-in-water nanoemulsion.
Nanomedicine 2018 May
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.
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.
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