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Oral lipid-based formulations alter delivery of cannabidiol to different anatomical regions in the brain

Brookes, Alice; Jewell, Adelaide; Feng, Wanshan; Bradshaw, Tracey D.; Butler, James; Gershkovich, Pavel

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Authors

Alice Brookes

Adelaide Jewell

Wanshan Feng

James Butler



Abstract

Delivery to the brain is a challenging task due to its protection by the blood–brain barrier (BBB). Lipids and fatty acids are reported to affect the permeability of the BBB, although this has not been reported following oral administration. Cannabidiol (CBD) has high therapeutic potential in the brain, therefore, this work investigated CBD delivery to anatomical brain regions following oral administration in lipid-based and lipid-free vehicles. All formulations resulted in a short brain Tmax (1 h) and brain-plasma ratios ≥ 3.5, with retention up to 18 h post administration. The highest CBD delivery was observed in the olfactory bulb and striatum, and the medulla pons and cerebellum the lowest. The lipid-free vehicle led to the highest levels of CBD in the whole brain. However, when each anatomical region was assessed individually, the long chain triglyceride-rich rapeseed oil formulation commonly showed optimal performance. The medium chain triglyceride-rich coconut oil formulation did not result in the highest CBD concentration in any brain region. Overall, differences in CBD delivery to the whole brain and various brain regions were observed following administration in different formulations, indicating that the oral formulation selection may be important for optimal delivery to specific regions of the brain.

Journal Article Type Article
Acceptance Date Jan 22, 2023
Online Publication Date Jan 28, 2023
Publication Date Mar 25, 2023
Deposit Date Feb 8, 2023
Publicly Available Date Feb 16, 2023
Journal International Journal of Pharmaceutics
Print ISSN 0378-5173
Electronic ISSN 1873-3476
Publisher Elsevier BV
Peer Reviewed Peer Reviewed
Volume 635
Article Number 122651
DOI https://doi.org/10.1016/j.ijpharm.2023.122651
Keywords Lipid-based drug delivery; Oral; Brain regions; Blood-brain barrier; Cannabidiol
Public URL https://nottingham-repository.worktribe.com/output/17079397
Publisher URL https://www.sciencedirect.com/science/article/pii/S0378517323000716?via%3Dihub

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