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- Title
Quantitative In Vitro and In Vivo Evaluation of Intestinal and Blood-Brain Barrier Transport Kinetics of the Plant N-Alkylamide Pellitorine.
- Authors
Veryser, Lieselotte; Bracke, Nathalie; Wynendaele, Evelien; Joshi, Tanmayee; Tatke, Pratima; Taevernier, Lien; De Spiegeleer, Bart
- Abstract
Objective. To evaluate the gut mucosa and blood-brain barrier (BBB) pharmacokinetic permeability properties of the plant N-alkylamide pellitorine. Methods. Pure pellitorine and an Anacyclus pyrethrum extract were used to investigate the permeation of pellitorine through (1) a Caco-2 cell monolayer, (2) the rat gut after oral administration, and (3) the BBB in mice after intravenous and intracerebroventricular administration. A validated bioanalytical UPLC-MS2 method was used to quantify pellitorine. Results. Pellitorine was able to cross the Caco-2 cell monolayer from the apical-to-basolateral and from the basolateral-to-apical side with apparent permeability coefficients between 0.6·10-5 and 4.8·10-5 cm/h and between 0.3·10-5 and 5.8·10-5 cm/h, respectively. In rats, a serum elimination rate constant of 0.3 h−1 was obtained. Intravenous injection of pellitorine in mice resulted in a rapid and high permeation of pellitorine through the BBB with a unidirectional influx rate constant of 153 μL/(g·min). In particular, 97% of pellitorine reached the brain tissue, while only 3% remained in the brain capillaries. An efflux transfer constant of 0.05 min−1 was obtained. Conclusion. Pellitorine shows a good gut permeation and rapidly permeates the BBB once in the blood, indicating a possible role in the treatment of central nervous system diseases.
- Subjects
AMIDES; ANIMAL experimentation; BIOLOGICAL assay; BIOLOGICAL transport; BLOOD-brain barrier; CAPILLARIES; CELL culture; DYNAMICS; HIGH performance liquid chromatography; INTRAVENOUS injections; INTESTINAL mucosa; MASS spectrometry; RESEARCH methodology; PERMEABILITY; RATS; RESEARCH funding; TISSUE culture; PLANT extracts; QUANTITATIVE research; DATA analysis software; DESCRIPTIVE statistics; IN vitro studies; INTRAVENTRICULAR injections; IN vivo studies
- Publication
BioMed Research International, 2016, Vol 2016, p1
- ISSN
2314-6133
- Publication type
Article
- DOI
10.1155/2016/5497402