Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid

Abstract

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.

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

“…In mice, 20 studies reported anxiety outcomes (Aso et al, 2019; Assareh et al, 2020; Breuer et al, 2016; Casarotto et al, 2010; Deiana et al, 2012; Florensa-Zanuy et al, 2021; Kasten et al, 2019; Long et al, 2010, 2012; Myers et al, 2019; Nardo et al, 2014; Navarrete et al, 2018; Onaivi et al, 1990; Schiavon et al, 2016; Todd and Arnold, 2016; Todd et al, 2017; Twardowschy et al, 2013; Uribe-Mariño et al, 2012; Zagzoog et al, 2020; Zieba et al, 2019) and four studies reported PK outcomes but no anxiety outcomes, or no CBD-vehicle comparison was reported (Anderson et al, 2021; Brzozowska et al, 2016; Majimbi et al, 2021; Pang et al, 2021). In two studies, both types of outcomes were reported (Deiana et al, 2012; Zieba et al, 2019).…”

“…This has been demonstrated for rats (Cherniakov et al, 2017: 27) and humans (Taylor et al, 2018: 1061), but to a lesser extent for mice; Pang et al (2021: 2044) reported no differences in T max between six mice. In addition, T max strongly depends on the formulation used in rats (Cherniakov et al, 2017: 27), mice (Majimbi et al, 2021: 8) and humans (Izgelov, Davidson et al, 2020a: 3). Thus, in some cases, the anxiety test may have already been terminated at the time plasma levels of CBD have reached their peak.…”

“…Second, we accounted for type of formulation and diet in our imputations of missing PK data with oral administration of CBD in humans, because C max (like T max ) depends on the formulation used (Cherniakov et al, 2017: 27; Izgelov et al, 2020a: 3; Majimbi et al, 2021: 8). Furthermore, evidence exists that PK parameters in humans are affected by food intake (Taylor et al, 2018: 1064).…”

Novel Nanoencapsulation Technology and its Potential Role in Bile Acid‐Based Targeted Gene Delivery to the Inner Ear

“…[101] Bile acids are widely used to improve drug delivery, including by improving transport across membranes, improving capsule strength and increasing drug release. [102][103][104][105][106] For example, deoxycholic acid, a secondary bile acid, has been shown to improve transport across the blood-brain barrier. [107] This may be useful in transportation across the blood labyrinthine barrier that connects the inner ear to the vasculature; to date however, this has not been established in the literature.…”

The Effect of Deoxycholic Acid on Chitosan-Enabled Matrices for Tissue Scaffolding and Injectable Nanogels

“…Naturally occurring secondary bile acid, namely deoxycholic acid (DCA), was found to exert positive and stabilising effects on nanogel capsules for oral delivery of a hydrophobic drug [ 24 ]. Majimbi et al observed greater bioavailability of cannabinol when administered in the form of DCA-enhanced microcapsules [ 25 ]. Li et al designed DCA-based micelles for targeted drug delivery of an antitumor agent [ 26 ].…”