MIT researchers have designed an innovative implantable drug-delivery device aimed at preventing the recurrence of glioblastoma, an aggressive brain tumor. This new technology utilizes ultrasound to enhance drug distribution within the brain following surgical tumor removal.
CAMBRIDGE, MA — Researchers at the Massachusetts Institute of Technology (MIT) have developed a groundbreaking implantable drug-delivery device designed to reduce the recurrence of glioblastoma, a highly aggressive type of brain tumor. Glioblastoma accounts for approximately 12-15% of all brain tumors and is associated with a grim prognosis; patients typically survive only 12 to 15 months post-diagnosis. The innovative device could be implanted during surgical procedures aimed at tumor removal, subsequently releasing drugs directly into the brain to target residual cancer cells.
Device Functionality and Design
The new device, known as the Long-term Ultrasound-enhanced Convective Injection Device (LUCID), features a reservoir capable of releasing therapeutic agents over an extended period. It includes an array of 24 ultrasound transducers that utilize sound waves to enhance drug distribution, allowing for improved penetration into the brain tissue and bypassing the blood-brain barrier. Canan Dagdeviren, an associate professor of media arts and sciences at MIT and the senior author of the study, articulated the device’s capabilities, stating, “We have 24 transducers in one ultrasound array, which can help a given drug bypass the blood-brain barrier and enhance the drug infusion.”
The device is designed to be flexible and as thin as a sheet of cardstock, with a drug-delivery cannula 3D-printed directly onto the ultrasound array. This design enables ultrasound waves to be generated precisely at the tip of the needle, facilitating the dispersion of drug molecules throughout a larger area of brain tissue during infusion.
Clinical Context and Implications
Glioblastoma, while rare, is one of the most lethal cancers diagnosed in the United States, with more than 10,000 new cases reported annually. Current treatment protocols typically involve surgical resection of the tumor followed by radiation and chemotherapy. Standard chemotherapy methods, including oral medications and intravenous infusions, often lead to significant side effects and limited efficacy in targeting tumor cells effectively. New methods, such as drug-delivery wafers and hydrogels, have emerged in recent years, allowing for localized treatment that minimizes systemic toxicity. However, these existing technologies rely on passive diffusion and lack the precise control of drug release timing that LUCID offers.
The study’s lead authors, MIT graduate student Sarah Ornellas and PhD candidate Jason Hou, emphasized the importance of ultrasound in their research. Previous studies indicated that ultrasound enhances the distribution of drug molecules by creating convective flows that allow for greater dispersion distances. Additionally, ultrasound waves can temporarily increase the permeability of the blood-brain barrier, facilitating drug entry into the brain.
Testing and Results
The functionality of the LUCID device was tested in both tissue models and a mouse study. In a tissue phantom designed to mimic human brain tissue, the researchers demonstrated that ultrasound-assisted delivery significantly increased the distance that drug molecules spread compared to traditional delivery methods without ultrasound. When the ultrasound array was activated in mouse models, it was observed that a contrast agent used in MRI scans spread more extensively through the brain, further validating the device’s efficacy.
The implant’s reservoir can hold approximately 100 microliters of fluid, and drug delivery is facilitated by a passive osmotic pump. The ultrasound component can be controlled wirelessly via Bluetooth, and the device is equipped with a small rechargeable battery.
Future Applications and Research
Looking ahead, the researchers suggest that the technology behind LUCID could extend beyond glioblastoma treatment to include other soft tissue interventions and delivery of various therapeutic agents, including immunotherapies and gene therapies. Dagdeviren noted, “We started with the brain as a follow-up to our ImPULS technology, but eventually this can be used for other soft tissue treatments for different types of drugs, different types of interventions in deep body tissue.”
The research findings were published in the journal Device, and the study was funded by the MIT Media Lab Consortium and the National Institutes of Health. This innovative device represents a significant advancement in the field of brain cancer treatment, offering hope for improved patient outcomes and greater control over drug delivery mechanisms.
Other contributors to the study include Michal Nowicki from Massachusetts General Hospital, Jerry Li, a recent Harvard graduate, and researchers from Boston University and Harvard Medical School. As the research progresses, further studies will be required to explore the device’s long-term efficacy and safety in human subjects.
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