Computationally Guided Intracerebral Drug Delivery via Chronically Implanted Microdevices.

Cell Reports
Khalil B RamadiMichael J Cima

Abstract

Treatments for neurologic diseases are often limited in efficacy due to poor spatial and temporal control over their delivery. Intracerebral delivery partially overcomes this by directly infusing therapeutics to the brain. Brain structures, however, are nonuniform and irregularly shaped, precluding complete target coverage by a single bolus without significant off-target effects and possible toxicity. Nearly complete coverage is crucial for effective modulation of these structures. We present a framework with computational mapping algorithms for neural drug delivery (COMMAND) to guide multi-bolus targeting of brain structures that maximizes coverage and minimizes off-target leakage. Custom-fabricated chronic neural implants leverage rational fluidic design to achieve multi-bolus delivery in rodents through a single infusion of radioactive tracer (Cu-64). The resulting spatial distributions replicate computed spatial coverage with 5% error in vivo, as detected by positron emission tomography. COMMAND potentially enables accurate, efficacious targeting of discrete brain regions.

References

May 1, 1980·Journal of Neuropathology and Experimental Neurology·R ZaczekJ T Coyle
Mar 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·M R KilbournJ T Greenamyre
Jan 15, 2003·Neurology·J G NuttUNKNOWN ICV GDNF Study Group. Implanted intracerebroventricular. Glial cell line-derived neurotrophic factor
Feb 26, 2005·Annals of Neurology·Charles H ViteJohn H Wolfe
Sep 12, 2006·Experimental Neurology·Michael F SalvatoreDon M Gash
Jan 11, 2007·Archives of Neurology·Mahlon R DeLong, Thomas Wichmann
Apr 5, 2007·Nature Protocols·Ali CetinPavel Osten
Oct 29, 2008·The International Journal of Medical Robotics + Computer Assisted Surgery : MRCAS·L RamrathA Schweikard
May 27, 2009·Nature Reviews. Neuroscience·Benno RoozendaalSumantra Chattarji
Sep 30, 2009·Journal of Neuroscience Methods·Tomasz BlasiakMarian H Lewandowski
Dec 22, 2009·Journal of Neurosurgery·John H SampsonUNKNOWN PRECISE Trial Investigators
Jul 5, 2011·Neuroscience·T Wichmann, J O Dostrovsky
Jul 13, 2011·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Miu Fei LamChristopher R P Lind
Sep 24, 2011·Neuroscience·M E RiceS J Cragg
Apr 10, 2012·Nature Neuroscience·Ken-ichi Amemori, Ann M Graybiel
Jun 12, 2012·Neuron·Mitsuko Watabe-UchidaNaoshige Uchida
Jun 13, 2012·Epilepsy & Behavior : E&B·Daniel J CurryAngus A Wilfong
Jan 10, 2013·Molecular Pharmaceutics·Daniel J Wolak, Robert G Thorne
May 23, 2014·Brain : a Journal of Neurology·Claudio PolloMichael Schüpbach
Jan 17, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Erik CederfjällDeniz Kirik
Jan 23, 2016·Nature Reviews. Drug Discovery·William A Banks
Feb 24, 2016·Frontiers in Neuroscience·Marc V Fuccillo
May 30, 2017·International Journal of Medical Sciences·Lizheng WangXianghui Yu
Jan 26, 2018·Science Translational Medicine·Canan DagdevirenRobert Langer
May 26, 2018·Molecular Genetics and Metabolism·Irene SlavcManfred Westphal
Jun 27, 2018·Proceedings of the National Academy of Sciences of the United States of America·Khalil B RamadiMichael J Cima
Jul 24, 2018·Frontiers in Behavioral Neuroscience·Lívea Dornela GodoyEduardo Henrique de Lima Umeoka

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.