Targeted Drug Delivery to the Brain Using Focused Ultrasound

Abstract

Drug delivery to the brain remains a challenging field. The presence of a physiological barrier, the blood-brain barrier (BBB), complicates the delivery of drugs to the brain. Although several methods have been developed for drug delivery to the brain, they have problems such as being invasive or lacking in target specificity. On the other hand, ultrasound has emerged as a treatment method and a diagnostic technology. Several studies have shown the feasibility of using ultrasound for the localized and reversible disruption of the BBB. In this review, I would like to review the recent advancement of ultrasound-induced MRI-guided BBB disruption technique and other methods for delivering drugs to the brain.

The Role of Caveolin-1 in Blood–Brain Barrier Disruption Induced by Focused Ultrasound Combined with Microbubbles

“…MB microbubbles, FUS focused ultrasound collapse of the microbubbles triggered by ultrasound causes transient enhancement of cell membrane permeability (Deng et al 2004). Moreover, this finding could strengthen the hypothesis that ultrasound-induced BBB disruption was triggered by the cavitation of microbubbles within the brain microvasculature, which probably activated the transcellular pathways across endothelial cells (Sheikov et al 2004;Hynynen et al 2005;Kinoshita 2006). When microbubbles were subjected to an ultrasonic field, they could have experienced either stable or inertial cavitation.…”

“…When microbubbles were subjected to an ultrasonic field, they could have experienced either stable or inertial cavitation. Stable cavitation refers to a condition in which microbubbles oscillate within the ultrasonic field, and inertial cavitation is a condition in which microbubbles violently collapse (Kinoshita 2006). Microbubbles irradiated by FUS with the specific parameters that we used could cause stable cavitation, but not inertial cavitation.…”

Intracranial Applications of Magnetic Resonance-guided Focused Ultrasound

“…Such compounds can include chemotherapy agents, as well as monoclonal antibodies. The last decade has seen significant advances in this area, with preclinical models demonstrating 1) that MRgFUS can open the BBB temporarily while not generating a lesion or irreversible damage [21]; 2) that chemotherapy agents can get into the brain in concentrations that correlate with the time that the BBB was open [59,60]; 3) that temporary BBB opening is safe in small-and medium-sized animals [20,21,61]; and 4) that it is possible to achieve significant levels of concentration in various types of tumors, including gliomas and brain metastases [62].…”

Detecting blood–brain barrier disruption within minimal hemorrhage following transcranial focused ultrasound: A correlation study with contrast‐enhanced MRI

“…This increase in BBB permeability can be detected by contrast-enhanced MRI using gadolinium-based (8,9) or iron oxide-based contrast agents (10) or by single-photon emission computed tomography with 99m Tc-based radiotracers (11). Using these imaging methods to guide FUS sonication, BBB at the targeted brain regions can be disrupted accurately, facilitating the delivery of diagnostic or therapeutic agents (12)(13)(14)(15)(16)(17).Although FUS sonication is promising in facilitating drug delivery across BBB, increasing concerns have been raised regarding its potential adverse effects on the brain. Indeed, FUS sonication could damage the brain tissue via FUS-induced edema, hemorrhage, ischemia, and apoptosis (10,18,19).…”

“…This increase in BBB permeability can be detected by contrast-enhanced MRI using gadolinium-based (8,9) or iron oxide-based contrast agents (10) or by single-photon emission computed tomography with 99m Tc-based radiotracers (11). Using these imaging methods to guide FUS sonication, BBB at the targeted brain regions can be disrupted accurately, facilitating the delivery of diagnostic or therapeutic agents (12)(13)(14)(15)(16)(17).…”