Neurological disorders and diseases of the brain are increasingly prevalent health concerns due to an aging population, increased awareness of long term effects of traumatic brain injury, and incidence of brain cancer. Treating the brain presents a unique challenge for due to the delicate nature of the tissue and privileged environment due to the blood-brain barrier. Drug delivery systems have been used to ferry drugs to the brain and central nervous system (CNS), however cerebrospinal fluid (CSF) turnover can rapidly clear drugs from the CNS and reduce treatment efficacy. This proposal will explore strategies to locally deliver drugs to the brain and reduce drug efflux by modulating CSF production. This proposal will test the hypothesis that CSF dynamics affect drug exposure in the CNS. During the mentored phase, I will learn device fabrication techniques and develop drug delivery micro devices capable of locally delivering multiple compounds into the brain parenchyma. Development of these devices is necessary, as many drugs do not efficiently cross into the brain when administered systemically. I will use these devices and in vivo imaging techniques to quantify how CSF-modulating drugs such as acetazolamide affect drug distribution and exposure. The data and skills acquired during the mentored phase will lead to the evaluation of CSF-modulating drug delivery systems in rodent models of brain cancer during the independent phase of this grant. During the independent phase, I will combine my background in chemistry and animal models of disease with newly learned fabrication expertise and explore the relationship between reducing CSF efflux of drugs and treatment efficacy in rodent models of brain disease. I will test the effectiveness of these drug delivery systems using rodent models of brain cancer and design new, molecular delivery vehicles. This line of research will lead to more effective ways to treat brain cancers, neurodegenerative diseases, and other diseases of the brain.

Public Health Relevance

Neurological disorders and diseases of the brain are difficult to treat since drugs fail to reach high concentrations in the brain and are rapidly cleared. This grant proposes the development of two micro scale drug delivery devices that can be implanted in the brain and modulate how drugs are cleared from the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Transition Award (R00)
Project #
5R00EB016690-04
Application #
9206158
Study Section
Special Emphasis Panel (NSS)
Program Officer
Rampulla, David
Project Start
2016-01-15
Project End
2018-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Rutgers University
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
001912864
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Spencer, Kevin C; Sy, Jay C; Falcón-Banchs, Roberto et al. (2017) A three dimensional in vitro glial scar model to investigate the local strain effects from micromotion around neural implants. Lab Chip 17:795-804
Spencer, Kevin C; Sy, Jay C; Ramadi, Khalil B et al. (2017) Characterization of Mechanically Matched Hydrogel Coatings to Improve the Biocompatibility of Neural Implants. Sci Rep 7:1952