title: Ultrasound-induced blood-brain barrier opening for drug delivery.
abstract: Treatment of central nervous system (CNS) diseases is highly limited due to the presence of the blood-brain barrier (BBB), which prevents the entry of approximately 99% of potential therapeutic agents into the CNS. Focused ultrasound (FUS) in combination with microbubbles can lead to a transient and focal opening of the BBB, thus enabling the passage of therapeutic agents across the BBB. Mechanical ultrasound effects, such as stable and inertial cavitation, contribute to BBB opening, possibly via transient disintegration of tight junctions. Facilitation of transcellular passage through vesicle transport may also be influenced. FUS-induced BBB opening can be performed without tissue damage, given an optimal set of ultrasound parameters. However, the risk of parenchymal damage or microhaemorrhage increases with increasing acoustic energy. To date, several therapeutic substances, such as chemotherapeutics, antibodies, plasmids and viral vectors, have successfully been delivered to the CNS by FUS-induced BBB opening in animal models, including non-human primates. Translation to a clinical application is pending.
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Alonso
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006801:Humans; D008279:Magnetic Resonance Imaging; D045423:Microbubbles / Q000627:therapeutic use*