Targeted drug delivery to the brain
The BBB is a semi-permeable barrier that separates the blood from the central nervous system’s (CNS) extracellular fluid. It consists of endothelial cells linked by tight junctions that selectively permit the transfer of amino acids and glucose, as well as the diffusion of water and lipophilic molecules. Although it serves as the gatekeeper of the brain by preventing harmful substances from reaching the brain, at the same time it blocks the delivery of many therapeutics. To address this, scientists of the EU-funded MRGFUS IN THE BRAIN (Focused ultrasound under magnetic resonance guidance for targeted drug delivery in the brain) project proposed to temporarily disrupt the BBB by using focused ultrasound in combination with microbubbles. The aim was to improve the delivery of therapeutics such as antibody therapies already approved in humans for the treatment of extracranial metastases from HER2-positive breast cancer. Researchers focused ultrasound at the location of the tumour under magnetic resonance (MR) guidance, thereby disrupting the BBB only locally. They tested the approach in healthy rats, and demonstrated that the BBB could be disrupted repeatedly without significant damage to the brain when low acoustic pressures were used. Rats with brain metastases from breast cancer treated with a combination of focused ultrasound and antibody therapy exhibited tumour growth inhibition during the treatment period. Despite the partial in vivo efficacy of the approach, researchers are confident that MR-guided focused ultrasound is a promising technique for targeted drug delivery in the brain for treating various diseases of the CNS. Towards this goal, the consortium expanded the equipment and imaging protocols so as to continue investigating the possibilities for enhanced drug delivery using BBB disruption with focused ultrasound.
Keywords
Blood brain barrier, MRGFUS IN THE BRAIN, focused ultrasound, antibody therapies, breast cancer
