Increased Vascular Permeability

Physiological barriers exist between the interior of blood vessels and their surrounding tissue, which can limit delivery of drugs to their intended targets. Focused ultrasound can reversibly increase the permeability of blood vessel walls, thereby temporarily allowing drugs to pass through them and into the surrounding tissue.

The delivery of drugs across vessel walls is limited primarily by a network of endothelial cells joined by tight junctions. The mechanical effects of focused ultrasound disrupt these tight junctions to increase permeability. Microbubbles are used to better control this process to reduce the risk of damage to the vessel.

This same effect has been used to open the blood-brain barrier, a particularly dense barrier of cells that severely inhibits the diffusion of many therapeutics into the brain. In both preclinical and clinical research, focused ultrasound coupled with intravenously injected microbubbles has been used to transiently open this barrier and enable delivery of various compounds into the brain. The blood-brain barrier has been shown, via both MRI and histological analyses, to revert to its original structure without permanent damage within four hours after the end of the sonication.

This technique could enable more effective pharmacological treatment of tumors throughout the body, and through blood-brain barrier opening, the treatment of various neurological disorders such as Parkinson’s disease, Alzheimer’s disease, and glioblastoma.

Click here for additional references from PubMed.