School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
GlaxoSmithKline Research and Development, Park Road, Ware, Hertfordshire SG12 0DP, UK.
Int J Pharm. 2023 Mar 25;635:122651. doi: 10.1016/j.ijpharm.2023.122651. Epub 2023 Jan 28.
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 (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.
由于血脑屏障（BBB）的保护，将药物递送到大脑是一项具有挑战性的任务。据报道，脂质和脂肪酸会影响 BBB 的通透性，尽管这尚未在口服给药后得到报道。大麻二酚（CBD）在大脑中有很高的治疗潜力，因此，这项工作研究了在脂质和无脂质载体中口服给药后 CBD 向解剖脑区的递送。所有制剂在 1 小时内使脑 T（1h）和脑-血浆比≥3.5，给药后 18 小时内仍有保留。在嗅球和纹状体中观察到 CBD 的递送最高，而在延髓脑桥和小脑最低。无脂质载体导致整个大脑中 CBD 水平最高。然而，当单独评估每个解剖区域时，富含长链甘油三酯的菜籽油制剂通常表现出最佳性能。富含中链甘油三酯的椰子油制剂并未使任何脑区的 CBD 浓度达到最高。总体而言，在不同制剂中给药后，CBD 向整个大脑和不同脑区的递送存在差异，这表明口服制剂的选择可能对向大脑特定区域的最佳递送很重要。
