@article{4c21a8c5409f4fbd9e13b61674e2817b,
title = "Miniaturized neural system for chronic, local intracerebral drug delivery",
abstract = "Recent advances in medications for neurodegenerative disorders are expanding opportunities for improving the debilitating symptoms suffered by patients. Existing pharmacologic treatments, however, often rely on systemic drug administration, which result in broad drug distribution and consequent increased risk for toxicity. Given that many key neural circuitries have sub–cubic millimeter volumes and cell-specific characteristics, small-volume drug administration into affected brain areas with minimal diffusion and leakage is essential. We report the development of an implantable, remotely controllable, miniaturized neural drug delivery system permitting dynamic adjustment of therapy with pinpoint spatial accuracy. We demonstrate that this device can chemically modulate local neuronal activity in small (rodent) and large (nonhuman primate) animal models, while simultaneously allowing the recording of neural activity to enable feedback control.",
author = "Canan Dagdeviren and Ramadi, {Khalil B.} and Pauline Joe and Kevin Spencer and Schwerdt, {Helen N.} and Hideki Shimazu and Sebastien Delcasso and Amemori, {Ken Ichi} and Carlos Nunez-Lopez and Graybiel, {Ann M.} and Cima, {Michael J.} and Robert Langer",
note = "Funding Information: We thank P. Bhagchandani and Z. Wei for technical support during device fabrication and S. C. Dagdeviren for the useful suggestions in device design. We acknowledge the cleanroom facilities of Harvard University Center for Nanoscale Systems and MIT Microsystems Technology Laboratories. We thank H. Mak and the Animal Imaging Core Facility at the Koch Institute for Integrative Cancer Research for help with PET imaging and the facility access, respectively. Funding: This study was supported by the NIH, National Institute of Biomedical Imaging and Bioengineering (R01 EB016101 to R.L., A.M.G., and M.J.C.). Author contributions: C.D. designed and fabricated the MiNDS. P.J. assisted on MiNDS fabrication steps. C.D., K.B.R., A.M.G., M.J.C., and R.L. designed in vitro pump and PET studies and in vivo small- and large-animal model experiments. K.B.R., P.J., and K.S. conducted biocompatibility studies. K.B.R., C.D., P.J., K.S., and C.N.-L. designed and conducted in vitro pump characterization. K.B.R. and K.S. performed rodent surgeries, PET studies, and behavioral studies on rat models. K.S. and S.D. conducted tetrode trials on rat models. H.N.S., H.S., and K.-i.A. performed NHP surgeries and in vivo drug infusion trials in NHP. All authors discussed, analyzed, interpreted the results, and wrote and edited the manuscript. Competing interests: C.D., M.J.C., and R.L. Publisher Copyright: Copyright {\textcopyright} 2018 The Authors, some rights reserved.",
year = "2018",
month = jan,
day = "24",
doi = "10.1126/scitranslmed.aan2742",
language = "English (US)",
volume = "10",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "425",
}