Development of Skull-Implanted Ultrasound for Blood-Brain Barrier Opening and Drug Delivery in Neuro-Oncology

The blood-brain barrier (BBB) poses a significant challenge for the treatment of brain tumors as it limits the passage of most circulating drugs into the brain. Low-intensity ultrasound with microbubbles safely and transiently opens the blood-brain barrier, improving drug delivery to the brain. Skull-implanted ultrasound devices are particularly effective as they allow ultrasound waves to bypass the skull. Additionally, this technology has enabled sonication procedures to be performed without the need for real-time imaging guidance, neuronavigation or MRI. Here, we review recent advancements in skull-implanted ultrasound for BBB opening and drug delivery in neuro-oncology. We highlight key preclinical and clinical studies demonstrating the safety of repeated BBB opening using skull-implanted ultrasound devices and discuss the expanding field with the activation of up to nine implanted ultrasound emitters simultaneously. We also summarize pharmacokinetic studies supporting the efficacy of this strategy for enhanced drug delivery to the brain. Additionally, we examine evidence on the temporal dynamics of BBB restoration post-sonication in brain tumor patients, emphasizing the importance of optimizing drug delivery timing. Lastly, we address current challenges and explore future directions for this promising therapeutic strategy.