Development and Evaluation of Brain-targeted Drug and Gene Delivery System

New drug modalities such as nucleic acid, gene, cells, and nanoparticles are expected for treating refractory diseases. However, these drugs have larger size and low cell membrane permeability; therefore, drug delivery systems (DDS) are essential for delivery to the intended site at the organ and cellular level. In case of the brain, drug migration to the brain from blood circulation is extremely limited by the blood-brain barrier (BBB). Therefore, brain-targeted DDS technologies with the ability to overcome the BBB are being intensively developed. Ultrasound-mediated BBB opening can transiently permeabilize the BBB via cavitation and oscillation and is expected to transfer drugs into the brain. Besides several fundamental studies, clinical studies on BBB opening have also been undertaken, proving its efficacy and safety. Our group has developed an ultrasound-mediated DDS to the brain for low-molecular weight drugs as well as plasmid DNA and mRNA intended for gene therapy. We also evaluated the distribution of gene expression to obtain essential information for applying gene therapy. Here, I provide general information on DDS to the brain, and describe our research progress in brain-targeted delivery of plasmid DNA and mRNA using BBB opening.