PLoS One. 2021 Jun 17;16(6):e0243858. doi: 10.1371/journal.pone.0243858. eCollection 2021.
BACKGROUND: Cannabidiol (CBD) confers therapeutic effects in some neurological disorders via modulation of inflammatory, oxidative and cell-signalling pathways. However, CBD is lipophilic and highly photooxidative with low oral bioavailability in plasma and brain. In this study, we aimed to design and test a CBD microencapsulation method as a drug delivery strategy to improve the absorption of CBD. Additionally, we evaluated the brain uptake of CBD capsules when administered alongside capsules containing a permeation-modifying bile acid, deoxycholic acid (DCA).
METHODS: Microcapsules containing either CBD or DCA were formed using the ionic gelation method with 1.5% sodium alginate formulations and 100 mM calcium chloride. C57BL/6J wild type mice randomly assigned to three treatment groups (3-4 mice per group) were administered CBD in the following preparations: 1) CBD capsules, 2) CBD capsules + DCA capsules and 3) naked CBD oil (control). To assess the short-term bioavailability of CBD, plasma and brain samples were collected at 0.3, 1 and 3 hours post administration and CBD levels were analysed with liquid chromatography mass spectrometer.
RESULTS: We produced spherical capsules at 400 ± 50 μm in size. The CBD capsules were calculated to have a drug loading of 2% and an encapsulation efficiency of 23%. Mice that received CBD capsules + DCA capsules showed a 40% and 47% increase in CBD plasma concentration compared to mice on CBD capsules and naked CBD oil, respectively. Furthermore, the CBD capsules + DCA capsules group showed a 48% and 25% increase in CBD brain concentration compared to mice on CBD capsules and naked CBD oil, respectively. In mice treated with CBD capsules + DCA capsules, the brain CBD concentration peaked at 0.3 hours with a 300% increased availability compared to CBD capsules and naked CBD oil groups, which peaked at 1 hour after administration.
CONCLUSIONS: The microencapsulation method combined with a permeation enhancer, DCA increased the short-term bioavailability of CBD in plasma and brain.