Researchers cross blood-brain barrier with glucose

Researchers cross blood-brain barrier with glucose
Immunofluorescence histologies of rat hippocampus sections of animals treated with asymmetric LA-coated carriers (credit: Joseph et al)

A new drug delivery system that autonomously navigates the body using its own glucose molecules has been developed and tested by a UCL-led team of scientists.

The study – published in Science Advances and funded by the European Research Council – demonstrates a new propulsion and guidance system for targeting drug delivery to the brain.

It is based on ‘chemotaxis’ whereby organisms naturally move towards or away from specific chemicals.

The system, tested in rats, successfully delivered drugs across the blood-brain barrier which is impermeable to many substances, making the brain difficult to treat.

The scientists say it could be adapted to deliver drugs to other areas in the body using other molecules in the body.

The carriers are made from biocompatible materials so don’t cause an inflammatory response from the body. Their movement in combination with the blood flow and the tissue architecture allows them to directly access nearly every site of the human body through blood vessels.

Current drug delivery systems use carrier particles with a similar basic structure but because their movement isn’t powered, the large majority accumulates in the centre of blood vessels. In contrast, the new carriers can escape the blood flow and accumulate at the vessel wall in the presence of a glucose gradient.

This increases the probability to interact with the natural machinery that allows access to the brain increasing considerably the crossing into its interior.

The carriers are made from two types of polymer that self-assemble into asymmetric spheres and this irregularity in shape was found to be important for driving the self-propulsion.

The team mapped the movement of symmetrical and asymmetrical carriers in the presence of glucose gradients and found that while the symmetric carriers diffuse randomly, the asymmetric carriers move towards the glucose source.

Tests were conducted to understand the importance of using molecules to target specific brain tissues, as well as the impact of shape and enzymes to drive movement.

For this, asymmetric and symmetric carriers were coated with a molecule called LRP-1 targeting peptide Angiopep-2 (LA) and delivered to rats’ brains via the bloodstream either with or without enzymes against controls.

The carriers that were asymmetric in shape, coated with LA and delivered using the enzyme powered mechanism performed best, delivering ~25% of the injected dose to brain tissues.

Asymmetric carriers with the LA coating, but without enzymes to power movement delivered ~7% of the injected dose and symmetrical carriers with the LA coating and enzymes delivered ~5% of the injected dose.

The team are now working on developing the system for use in humans, with the aim of developing targeted treatments for brain cancer.