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12th June 2019
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Cannabis compound delivers

Anthony King, 12 June 2019

006 Cannabis plant

A component of cannabis could help ferry medications across the blood-brain barrier, researchers in Spain report. Cannabidiol (CBD) is a non-psychoactive compound suggested to have beneficial health effects for anxiety and epilepsy.

Researchers coated CBD onto lipid nanocapsules containing a fluorescent molecule to act like a Trojan horse so the molecules could slip across the blood brain barrier undetected (Molecular Pharmaceutics, doi: 10.1021/acs.molpharmaceut.8b01344 ).

CBD resembles endocannabinoids, cannabis-like compounds made in mammals, which have receptors in the brain and can move across the blood brain barrier. ‘We wanted to test if lipid nano-vehicles could be useful for crossing a healthy blood brain barrier,’ says first author Juan Aparicio-Blanco at Complutense University in Madrid, who collaborated with researchers at Open University in Milton Keynes. The CBD decoration enhances delivery because it binds to receptors located at the barrier. ‘The final goal would be to deliver therapies for brain tumours,’ says Aparicio-Blanco.

This blood-brain barrier has proved an imposing obstacle in delivering drugs to the brain. Water-soluble drugs can’t pass through the endothelial cells that line the blood vessels, and cell membranes pump foreign substances back into the blood. Drug delivery to the brain ‘is applicable to just about all the central nervous system diseases,’ says Lester Drewes, a BBB expert at the University of Minnesota, including epilepsy, Alzheimer’s, Parkinson’s, brain tumours, multiple sclerosis, traumatic brain injury, cerebrovascular and genetic brain diseases.

One approach to getting drugs into the brain is to create particles that include encapsulated drugs, so small they can penetrate into tissues. These nanoparticles can be 10 to 100nm across, whereas the smallest blood vessels are around 4000nm in diameter.

The Madrid group in future plans to encapsulate a first line and a second line therapy for treating brain tumours in the oily core of the lipid nanocapsule. Already, they packed the core with CBD. ‘We included cannabidiol in the core as a drug substance, because it has itself been proven to have some activity against human glioma cells,’ says Aparicio-Blanco. This could allow for sustained release of CBD in the brain.

Rather than load the nanocapsules with a medication, however, the researchers in this study packed them with a fluorescent molecule to track them. In experiments with human brain cells, the CBD-displaying nanocarriers passed more fluorescent molecules across the cells than those without CBD. When injected into healthy mice, the CBD-nanoparticles delivered about 2.5 times more of the fluorescent molecule to the animals’ brains.

‘The main innovation of this report is that a particular class of nanoparticle is coated with a chemical that is believed to stick to the surface of endothelial cells through interaction with specific membrane components on their surface. This then enables the particle to target the brain,’ Drewes explains. ‘The key is whether there is enough drug delivery to the site of action to cause a [therapeutic] response.’

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