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

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 a...

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Autores principales: Majimbi, Maimuna, Brook, Emily, Galettis, Peter, Eden, Edward, Al-Salami, Hani, Mooranian, Armin, Al-Sallami, Hesham, Lam, Virginie, Mamo, John C. L., Takechi, Ryusuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211198/
https://www.ncbi.nlm.nih.gov/pubmed/34138862
http://dx.doi.org/10.1371/journal.pone.0243858
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author Majimbi, Maimuna
Brook, Emily
Galettis, Peter
Eden, Edward
Al-Salami, Hani
Mooranian, Armin
Al-Sallami, Hesham
Lam, Virginie
Mamo, John C. L.
Takechi, Ryusuke
author_facet Majimbi, Maimuna
Brook, Emily
Galettis, Peter
Eden, Edward
Al-Salami, Hani
Mooranian, Armin
Al-Sallami, Hesham
Lam, Virginie
Mamo, John C. L.
Takechi, Ryusuke
author_sort Majimbi, Maimuna
collection PubMed
description 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.
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spelling pubmed-82111982021-06-29 Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid Majimbi, Maimuna Brook, Emily Galettis, Peter Eden, Edward Al-Salami, Hani Mooranian, Armin Al-Sallami, Hesham Lam, Virginie Mamo, John C. L. Takechi, Ryusuke PLoS One Research Article 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. Public Library of Science 2021-06-17 /pmc/articles/PMC8211198/ /pubmed/34138862 http://dx.doi.org/10.1371/journal.pone.0243858 Text en © 2021 Majimbi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Majimbi, Maimuna
Brook, Emily
Galettis, Peter
Eden, Edward
Al-Salami, Hani
Mooranian, Armin
Al-Sallami, Hesham
Lam, Virginie
Mamo, John C. L.
Takechi, Ryusuke
Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid
title Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid
title_full Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid
title_fullStr Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid
title_full_unstemmed Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid
title_short Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid
title_sort sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211198/
https://www.ncbi.nlm.nih.gov/pubmed/34138862
http://dx.doi.org/10.1371/journal.pone.0243858
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