University College London
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 toward 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.
“We made tiny particles that can carry drug molecules in the main compartment, but each has a separate sack that sits on the outside of the particle and contains enzymes that use glucose as a fuel to drive movement,” explains lead author Prof. Giuseppe Battaglia, UCL Chemistry and UCL Chemical Engineering.
“These tiny drug carriers move towards areas where there are high levels of glucose, transforming it into fuel for their own propulsion.”
The carriers are made from biocompatible materials so they 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 center 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.
Self-Assembling Polymer Carrier
The carriers are made from two types of polymers that self-assemble into asymmetric spheres. 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 toward 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 percent of the injected dose to brain tissues.
Asymmetric carriers with the LA coating, but without enzymes to power movement delivered ~7 percent of the injected dose, and symmetrical carriers with the LA coating and enzymes delivered ~5 percent of the injected dose.
The team is working on developing the system for use in humans, with the aim of developing targeted treatments for brain cancer.