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

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 T_max (1 h) and brain-plasma ratios ≥3.5, with retention up to 18 h post administration.

Highlights

• Cannabidiol delivery to the brain was achieved following oral administration.
• Brain delivery of cannabidiol was altered by the lipid-based formulation selected.
• Cannabidiol delivery to anatomical brain regions differed to the whole brain.

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.

2.1. Materials

Plant derived CBD was purchased from THC Pharm (Frankfurt, Germany). 4,4-Dichlorodiphenyultrichloroethane (DDT), sesame oil, coconut oil and rapeseed oil were purchased from Sigma Aldrich (Dorset, UK). High purity propylene glycol was purchased from VWR (Poole, UK). All other solvents and reagents used were of HPLC grade or higher and purchased from Fisher Scientific (Leicester, UK).

Read more

Alice Brookes, Adelaide Jewell, Wanshan Feng, Tracey D. Bradshaw, James Butler, Pavel Gershkovich, Oral lipid-based formulations alter delivery of cannabidiol to different anatomical regions in the brain, International Journal of Pharmaceutics, 2023, 122651, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2023.122651.