Image-guided non-invasive transcranial drug delivery
Problem: Lack of tools for non-invasive neuromodulation with temporal, spatial, and chemical specificity
The ability to noninvasively activate, silence, and provide receptor subtype specific neuromodulation with spatial specificity would greatly advance our ability to study brain circuits in vivo. Pharmacological manipulations have been crucial for advancing our understanding of the relationship between circuit activity and behavior 1–3. However systemic drug delivery can produce off target effects, and many potentially useful drugs cannot penetrate the blood brain barrier (BBB). Local drug delivery currently requires invasive methods such as injections, cannulae, and pumps that damage tissues and can confound results. Current electrical and magnetic methods of noninvasive neuromodulation such as transcranial magnetic stimulation have limited spatial specificity and lack the ability to reach deep brain structures. Focused ultrasound (FUS) can be targeted anywhere in the brain with high spatial resolution and used for direct neural stimulation, however both it and all other noninvasive methods lack chemical specificity. FUS (using different parameters) can be used to locally open the BBB and allow focal drug delivery, however this by itself lacks temporal control and drugs can cause systemic effects. Importantly, all noninvasive techniques lack independent confirmation of the site of neuromodulation and therefore have unknown accuracy.
Solution: A focused ultrasound (FUS) and nanocarrier platform for localized drug delivery in the brain with MRI feedback
A recent technological advance that is key to the success of this method is the development by our group of novel MRI-visible nanoclusters with unique properties. These nanoclusters are biocompatible, can encapsulate drugs, and change MRI contrast upon drug release, enabling independent confirmation of the site and amount of drug release. Nanocluster drug delivery allows neuromodulatory agents to remain inside a cluster, limiting biodistribution until reaching the desired site for drug release, thus protecting off-target locations from drug action. Nanoclusters will be delivered to target brain regions by FUS induced BBB opening. In addition, transcranial FUS can be used to activate release of neuromodulatory agents from nanoclusters, providing temporal control. This new platform will provide location specific neuromodulation with MRI feedback, enabling the investigation of relationships between circuit manipulations and behavioral outcomes in rodents and eventually humans.
Department(s) Involved: Biomedical Engineering, Cell, Developmental, & Integrative Biology, Neurobiology, Neurology, Neurosurgery, Pharmacology & Toxicology, Radiology
Date Posted: February 4, 2019 3:51:28 PM CST
Location: Birmingham Campus
Type of research: Basic science, Translational science, Behavioral Research
Audience: Undergraduate Student - Summer, Undergraduate Student - Academic Year, Medical Student - Summer, Medical Student - Scholarly Activity, Graduate or MD/PhD Student, Resident
Research Type: Basic science, Translational science, Behavioral Research
URL for more information: http://markbolding.com
mbolding@uab.edu
205-641-1398
The ability to noninvasively activate, silence, and provide receptor subtype specific neuromodulation with spatial specificity would greatly advance our ability to study brain circuits in vivo. Pharmacological manipulations have been crucial for advancing our understanding of the relationship between circuit activity and behavior 1–3. However systemic drug delivery can produce off target effects, and many potentially useful drugs cannot penetrate the blood brain barrier (BBB). Local drug delivery currently requires invasive methods such as injections, cannulae, and pumps that damage tissues and can confound results. Current electrical and magnetic methods of noninvasive neuromodulation such as transcranial magnetic stimulation have limited spatial specificity and lack the ability to reach deep brain structures. Focused ultrasound (FUS) can be targeted anywhere in the brain with high spatial resolution and used for direct neural stimulation, however both it and all other noninvasive methods lack chemical specificity. FUS (using different parameters) can be used to locally open the BBB and allow focal drug delivery, however this by itself lacks temporal control and drugs can cause systemic effects. Importantly, all noninvasive techniques lack independent confirmation of the site of neuromodulation and therefore have unknown accuracy.
Solution: A focused ultrasound (FUS) and nanocarrier platform for localized drug delivery in the brain with MRI feedback
A recent technological advance that is key to the success of this method is the development by our group of novel MRI-visible nanoclusters with unique properties. These nanoclusters are biocompatible, can encapsulate drugs, and change MRI contrast upon drug release, enabling independent confirmation of the site and amount of drug release. Nanocluster drug delivery allows neuromodulatory agents to remain inside a cluster, limiting biodistribution until reaching the desired site for drug release, thus protecting off-target locations from drug action. Nanoclusters will be delivered to target brain regions by FUS induced BBB opening. In addition, transcranial FUS can be used to activate release of neuromodulatory agents from nanoclusters, providing temporal control. This new platform will provide location specific neuromodulation with MRI feedback, enabling the investigation of relationships between circuit manipulations and behavioral outcomes in rodents and eventually humans.
Basic Information
Principle Investigator: Mark BoldingDepartment(s) Involved: Biomedical Engineering, Cell, Developmental, & Integrative Biology, Neurobiology, Neurology, Neurosurgery, Pharmacology & Toxicology, Radiology
Date Posted: February 4, 2019 3:51:28 PM CST
Location: Birmingham Campus
Type of research: Basic science, Translational science, Behavioral Research
Audience: Undergraduate Student - Summer, Undergraduate Student - Academic Year, Medical Student - Summer, Medical Student - Scholarly Activity, Graduate or MD/PhD Student, Resident
Research Type: Basic science, Translational science, Behavioral Research
URL for more information: http://markbolding.com
Contact Information
Mark Boldingmbolding@uab.edu
205-641-1398
