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

Maimuna Majimbi; Emily Brook; Peter Galettis; Edward Eden; Hani Al-Salami; Armin Mooranian; Hesham Al-Sallami; Virginie Lam; John C L Mamo; Ryusuke Takechi

doi:10.1371/journal.pone.0243858

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

PLoS One. 2021 Jun 17;16(6):e0243858. doi: 10.1371/journal.pone.0243858. eCollection 2021.

Authors

Maimuna Majimbi^{1

2}, Emily Brook^{1

3}, Peter Galettis⁴, Edward Eden⁴, Hani Al-Salami^{1

3}, Armin Mooranian^{1

3}, Hesham Al-Sallami⁵, Virginie Lam^{1

2}, John C L Mamo^{1

2}, Ryusuke Takechi^{1

2}

Affiliations

¹ Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
² School of Population Health, Faculty of Health Sciences, Curtin University, Perth, WA, Australia.
³ Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA, Australia.
⁴ School of Medicine and Public Health, University of Newcastle and The Australian Centre for Cannabinoid Clinical and Research Excellence, Newcastle, NSW, Australia.
⁵ School of Pharmacy, University of Otago, Otago, New Zealand.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Alginates / chemistry*
Animals
Biological Availability
Cannabidiol / administration & dosage
Cannabidiol / chemistry*
Cannabidiol / pharmacokinetics*
Capsules
Deoxycholic Acid / administration & dosage*
Drug Carriers / chemistry*
Male
Mice

Substances

Alginates
Capsules
Drug Carriers
Deoxycholic Acid
Cannabidiol

Grants and funding

Zelira Therapeutics Ltd provided financial support for the study to cover all experimental cost. The authors do not have any ownership of stocks or shares; paid employment or consultancy; or board membership; nor received any research grants; travel grants or honoraria for speaking or participation at meetings; research materials; or gifts from the company. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.