Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor

Sheng-Kai Wu; Chia-Lin Tsai; Yuexi Huang; Kullervo Hynynen

doi:10.3390/pharmaceutics13010015

Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor

Pharmaceutics. 2020 Dec 24;13(1):15. doi: 10.3390/pharmaceutics13010015.

Authors

Sheng-Kai Wu^{1

2}, Chia-Lin Tsai^{1

2

3}, Yuexi Huang^{1

2}, Kullervo Hynynen^{1

2

4}

Affiliations

¹ Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
² Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
³ Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
⁴ Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.

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.

Keywords: blood–brain barrier (BBB); blood–brain–tumor barrier (BBTB); central nervous system (CNS); convention-enhanced delivery (CED); focused ultrasound (FUS).

Publication types

Review