Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor.

Authors: Wu SK, Tsai CL, Huang Y, Hynynen K

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.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To review strategies for delivering therapeutics to brain tumors, emphasizing characterization of the BBB/BBTB and the mechanisms and preclinical/clinical progress of focused ultrasound–induced BBB modulation.

Disease model malignant brain tumors

Route of administration Intracerebral/intratumoral infusion via convection-enhanced delivery (catheter); intravenous (systemic circulation with focused ultrasound)

Outcomes and Safety

Summary of Outcomes Focused ultrasound combined with systemically circulating microbubbles transiently increases BBB/BBTB permeability and enhances delivery of therapeutics to brain tumors; the review summarizes preclinical and clinical progress but does not report specific focused ultrasound parameter settings as being tested or identified as successful.

Safety-related matter The provided text does not mention any safety concerns, adverse effects, or toxicity related to the discussed delivery approaches.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

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