NEWS


PHARMACEUTICALS Cannabis compound delivers ANTHONY KING


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.


FOOD & AGRICULTURE Nematode RNAi nemesis ANTHONY KING


Parasitic nematode worms infect almost all cultivated crops, inflicting roughly a 20% loss in annual yields. Now, scientists have discovered metabolites in soil bacteria that protect crops against nematodes. Researchers in the Ukraine, and at the


University of Sussex, investigated the use of biostimulants from metabolites of soil Streptomycetes to protect wheat against the cereal cyst nematode Heterodera avenae (Frontiers in Plant Science, doi: 10.3389/ fpls.2019.00483). They found that the biostimulants boosted plant growth and development, and provided resistance against the nematode. University of Sussex mathematician


Konstantin Blyuss modelled the interaction between the bacterial metabolites, crop plants and nematodes and says that the metabolites or biostimulants work in two ways. ‘They target the nematode, turning off essential genes. In parallel, they also switch off some plant genes that facilitate entry of


the nematode.’ The cereal cyst nematode CCN is a patch


problem in UK cereals. ‘Pressure is probably increasing, mainly due to poor crop rotations where growers are not rotating crops in a field every season,’ explains Andy Evans, an agricultural pest scientist at Scotland’s Rural College in Edinburgh. Pesticide inputs kept nematode numbers in check, but most soil applied pesticides such as organophosphates are now withdrawn, and nematode populations are rising. ‘For some plant pathogenic nematode species in soil we have seen a 300% increase in populations over the last 15-20 years,’ says Evans. Lab investigations revealed that the biostimulants, obtained from Streptomycetes, churned out interference RNA that complemented messenger RNA (mRNA) from plants and their nematode foes. By binding to the strands of plant or pest mRNA, this complementary RNAi causes them to be degraded, stopping the mRNA passing on instructions to make a protein, by so-called ‘gene silencing’.


Plants react to nematodes feeding on their


roots by sending resources to root defence rather than investing in shoot and leaf growth, consequently plants become stunted with lower yields or uneven crop maturity. ‘There is huge potential for this strategy, but it needs to demonstrate efficacy in the field, and demonstrate no ‘trade-off’ in the crop such as reduced yields or crop quality,’ Evans explains. ‘They also need to figure out how best to apply this “technology”.’ How this RNAi technology will be regulated is another issue, he adds, questioning whether the approval process for chemical and biological pesticides will be appropriate. Gene silencing is triggered when the biostimulants are applied to seeds. Agro firm Bioinvest-Agro in Kiev is now producing products and selling them to small farming companies and large agribusinesses. ‘They have already been successfully used to grow wheat, rapeseed, soya, sunflower, corn as well as certain vegetables, such as cucumbers, tomatoes and peppers,’ according to Blyuss.


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.’


6 06 | 2019


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