Summary: Researchers have developed a cannabidiol (CBD) microcapsule that is absorbed faster and reaches the brain more rapidly in mouse models of neurological conditions such as Alzheimer’s disease, multiple sclerosis and traumatic brain injury.
Source: Curtin University
A research team led by Curtin University has developed a novel oral delivery method that significantly improves the short-term absorption and brain delivery of medicinal cannabis compounds. The formulation, based on microencapsulation of cannabidiol (CBD) and combined with a naturally occurring bile acid, shows promise for enhancing the effectiveness of CBD therapies for neurological disorders.
Published in the open-access journal PLOS ONE and supported by industry partner Zelira Therapeutics, the study demonstrates that small sodium alginate microcapsules containing CBD — when administered with capsules containing the bile acid deoxycholic acid (DCA) — produce faster systemic absorption and greater brain penetration in mouse models compared with unencapsulated CBD oil.
Lead investigator Associate Professor Ryu Takechi from the Curtin Health Innovation Research Institute (CHIRI) and the School of Population Health at Curtin University explained that CBD has therapeutic potential for a range of neurological and metabolic conditions but faces two major challenges when taken orally: poor absorption and vulnerability to light and stomach acid.
“Cannabidiol is a widely studied compound with reported benefits against inflammation, oxidative stress and dysregulated cell signalling in neurological disease. Still, its oral bioavailability is limited. Our goal was to design and test a practical drug delivery approach to improve how much CBD reaches the bloodstream and — crucially — the brain,” Associate Professor Takechi said.
The team employed sodium alginate microencapsulation to protect CBD from oxidation and light-induced degradation and to control release in the gastrointestinal tract. They also tested co-administration with deoxycholic acid, a bile acid known to modify intestinal permeability, to determine whether it could enhance CBD uptake into the circulation and across the blood–brain barrier.
“Using this encapsulation method together with a permeation enhancer, we observed a marked improvement in CBD delivery to the brain. In the animal experiments, brain availability of CBD increased substantially, and the drug was protected from rapid degradation, which also improves shelf life,” Associate Professor Takechi added.
Associate Professor Takechi emphasised that these preclinical results point to a promising strategy for improving oral CBD formulations for neurological indications, although further studies will be required to confirm safety and efficacy in humans.
Zelira Therapeutics’ CEO Dr Oludare Odumosu commented on the industry collaboration: “The new encapsulation technology substantially improves the efficiency with which cannabinoid-based drugs can be delivered into the brain. This could enhance the therapeutic effectiveness of cannabinoid treatments for neurological disorders while lowering costs and improving safety profiles.”
The research was a collaboration among investigators from the Curtin Health Innovation Research Institute (CHIRI), Curtin Medical School, Curtin’s School of Population Health, the University of Newcastle and the University of Otago.
About this CBD and neuropharmacology research news
Source: Curtin University
Contact: Lucien Wilkinson – Curtin University
Image: The image is in the public domain
Original Research: Open access. “Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid” by Ryu Takechi et al., PLOS ONE
Abstract
Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid
Background
Cannabidiol (CBD) can exert therapeutic effects in some neurological conditions by modulating inflammatory, oxidative and cell-signalling pathways. However, CBD is lipophilic and sensitive to photooxidation, leading to low oral bioavailability in both plasma and brain. The study aimed to create and test a CBD microencapsulation method to improve oral absorption and to evaluate whether co-administration with the permeation-modifying bile acid deoxycholic acid (DCA) enhances brain uptake.
Methods
Researchers prepared microcapsules containing either CBD or DCA using an ionic gelation technique with 1.5% sodium alginate and 100 mM calcium chloride. C57BL/6J wild-type mice were randomly allocated to three groups (three to four mice per group) and received one of the following oral preparations: 1) CBD microcapsules, 2) CBD microcapsules plus DCA microcapsules, or 3) unencapsulated CBD oil (control). To characterise short-term bioavailability, plasma and brain samples were collected at 0.3, 1 and 3 hours after dosing and analysed by liquid chromatography–mass spectrometry for CBD concentration.
Results
The team produced spherical microcapsules averaging about 400 ± 50 μm in diameter. The CBD-loaded capsules had a drug loading of approximately 2% and an encapsulation efficiency near 23%. Mice that received CBD capsules together with DCA capsules showed a 40% increase in plasma CBD concentration compared with mice given CBD capsules alone and a 47% increase compared with naked CBD oil. In the brain, CBD concentrations were 48% higher than with CBD capsules alone and 25% higher than with naked CBD oil when CBD and DCA capsules were co-administered. Notably, brain CBD levels in the CBD+DCA group peaked at 0.3 hours, showing a 300% greater availability at that early time point compared with the groups receiving CBD capsules alone or naked CBD oil, whose brain concentrations peaked at one hour post-dose.
Conclusions
Combining sodium alginate microencapsulation with a permeation enhancer, deoxycholic acid, increased the short-term oral bioavailability of cannabidiol in both plasma and brain in this preclinical model. These results support further investigation of encapsulation strategies and bile-acid-mediated permeation enhancement to improve oral CBD therapies for neurological disorders. Additional research is needed to evaluate translation to human clinical use.