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

<h4>Background</h4>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, w...

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Autores principales: Maimuna Majimbi, Emily Brook, Peter Galettis, Edward Eden, Hani Al-Salami, Armin Mooranian, Hesham Al-Sallami, Virginie Lam, John C L Mamo, Ryusuke Takechi
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:058676ea48c849268a27fc0338581c062021-11-25T06:23:31ZSodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid.1932-620310.1371/journal.pone.0243858https://doaj.org/article/058676ea48c849268a27fc0338581c062021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0243858https://doaj.org/toc/1932-6203<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>The microencapsulation method combined with a permeation enhancer, DCA increased the short-term bioavailability of CBD in plasma and brain.Maimuna MajimbiEmily BrookPeter GalettisEdward EdenHani Al-SalamiArmin MooranianHesham Al-SallamiVirginie LamJohn C L MamoRyusuke TakechiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0243858 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maimuna Majimbi
Emily Brook
Peter Galettis
Edward Eden
Hani Al-Salami
Armin Mooranian
Hesham Al-Sallami
Virginie Lam
John C L Mamo
Ryusuke Takechi
Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid.
description <h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>The microencapsulation method combined with a permeation enhancer, DCA increased the short-term bioavailability of CBD in plasma and brain.
format article
author Maimuna Majimbi
Emily Brook
Peter Galettis
Edward Eden
Hani Al-Salami
Armin Mooranian
Hesham Al-Sallami
Virginie Lam
John C L Mamo
Ryusuke Takechi
author_facet Maimuna Majimbi
Emily Brook
Peter Galettis
Edward Eden
Hani Al-Salami
Armin Mooranian
Hesham Al-Sallami
Virginie Lam
John C L Mamo
Ryusuke Takechi
author_sort Maimuna Majimbi
title 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_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_sort sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/058676ea48c849268a27fc0338581c06
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