Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor

Abstract

The presence of blood–brain barrier (BBB) and/or blood–brain–tumor barriers (BBTB) is one of the main obstacles to effectively deliver therapeutics to our central nervous system (CNS); hence, the outcomes following treatment of malignant brain tumors remain unsatisfactory. Although some approaches regarding BBB disruption or drug modifications have been explored, none of them reach the criteria of success. Convention-enhanced delivery (CED) directly infuses drugs to the brain tumor and surrounding tumor infiltrating area over a long period of time using special catheters. Focused ultrasound (FUS) now provides a non-invasive method to achieve this goal via combining with systemically circulating microbubbles to locally enhance the vascular permeability. In this review, different approaches of delivering therapeutic agents to the brain tumors will be discussed as well as the characterization of BBB and BBTB. We also highlight the mechanism of FUS-induced BBB modulation and the current progress of this technology in both pre-clinical and clinical studies.

Oncolytic virus in gliomas: a review of human clinical investigations

“…62 To overcome these challenges associated with intravascular OV delivery, methods of circumventing the BBB and neutralizing antibodies have been recently explored: mannitol infusions, focused ultrasound, and microbubble-mediated drug delivery systems are under active investigation. [62][63][64] Further modifying OVs either by genetic or chemical means is an active area of further investigation. 9 A recent report cites production of a recombinant measles virus with modifications that maintain oncolytic activity while evading anti-measles antibodies.…”

Emerging Nano-Carrier Strategies for Brain Tumor Drug Delivery and Considerations for Clinical Translation

“…In our view, passive uptake of liposomes alone is unlikely to become a game-changer for brain tumor treatment. However, focused transcranial ultrasound (FUS) and intravenous microbubbles, mentioned previously, may also be combined with nanomedicine therapy, pre-emptively disrupting the BBB prior to delivery of liposomal chemotherapeutics to brain tumors [ 51 , 77 ]. Ultrasound has been known to modulate the BBB since the 1950’s [ 78 ].…”

Advances in magnetic resonance imaging contrast agents for glioblastoma-targeting theranostics

“…Passive transport methods include simple diffusion and enhanced permeability and retention (EPR) effects, which do not consume energy. Other passive transport methods include the use of nanodrugs that block or bypass the BBB, such as the combination of focused ultrasound (FUS) with microbubbles (MBs) and convection-enhanced delivery (CED) [ 93–95 ].…”