Microfabricated infuse-withdraw micropump component for an integrated inner-ear drug-delivery platform

Verfasser / Beitragende:
[Vishal Tandon, Woo Seok Kang, Abigail Spencer, Ernest Kim, Erin Pararas, Michael McKenna, Sharon Kujawa, Mark Mescher, Jason Fiering, William Sewell, Jeffrey Borenstein]
Ort, Verlag, Jahr:
2015
Enthalten in:
Biomedical Microdevices, 17/2(2015-04-01), 1-16
Format:
Artikel (online)
ID: 605480419
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024 7 0 |a 10.1007/s10544-014-9923-8  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s10544-014-9923-8 
245 0 0 |a Microfabricated infuse-withdraw micropump component for an integrated inner-ear drug-delivery platform  |h [Elektronische Daten]  |c [Vishal Tandon, Woo Seok Kang, Abigail Spencer, Ernest Kim, Erin Pararas, Michael McKenna, Sharon Kujawa, Mark Mescher, Jason Fiering, William Sewell, Jeffrey Borenstein] 
520 3 |a One of the major challenges in treatment of auditory disorders is that many therapeutic compounds are toxic when delivered systemically. Local intracochlear delivery methods are becoming critical in emerging treatments and in drug discovery. Direct infusion via cochleostomy, in particular, is attractive from a pharmacokinetics standpoint, as there is potential for the kinetics of delivery to be well-controlled. Direct infusion is compatible with a large number of drug types, including large, complex molecules such as proteins and unstable molecules such as siRNA. In addition, hair-cell regeneration therapy will likely require long-term delivery of a timed series of agents. This presents unknown risks associated with increasing the volume of fluid within the cochlea and mechanical damage caused during delivery. There are three key requirements for an intracochlear drug delivery system: (1) a high degree of miniaturization (2) a method for pumping precise and small volumes of fluid into the cochlea in a highly controlled manner, and (3) a method for removing excess fluid from the limited cochlear fluid space. To that end, our group is developing a head-mounted microfluidics-based system for long-term intracochlear drug delivery. We utilize guinea pig animal models for development and demonstration of the device. Central to the system is an infuse-withdraw micropump component that, unlike previous micropump-based systems, has fully integrated drug and fluid storage compartments. Here we characterize the infuse-withdraw capabilities of our micropump, and show experimental results that demonstrate direct drug infusion via cochleostomy in animal models. We utilized DNQX, a glutamate receptor antagonist that suppresses CAPs, as a test drug. We monitored the frequency-dependent changes in auditory nerve CAPs during drug infusion, and observed CAP suppression consistent with the expected drug transport path based on the geometry and tonotopic organization of the cochlea. 
540 |a Springer Science+Business Media New York, 2015 
690 7 |a Drug Delivery  |2 nationallicence 
690 7 |a Microfluidics  |2 nationallicence 
690 7 |a Inner Ear  |2 nationallicence 
690 7 |a Intracochlear  |2 nationallicence 
690 7 |a CAP  |2 nationallicence 
690 7 |a DPOAE  |2 nationallicence 
690 7 |a Micropump  |2 nationallicence 
700 1 |a Tandon  |D Vishal  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
700 1 |a Kang  |D Woo Seok  |u Department of Otology and Laryngology Massachusetts Eye and Ear Infirmary and Harvard Medical School Boston, 02114, Boston, MA, USA  |4 aut 
700 1 |a Spencer  |D Abigail  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
700 1 |a Kim  |D Ernest  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
700 1 |a Pararas  |D Erin  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
700 1 |a McKenna  |D Michael  |u Department of Otology and Laryngology Massachusetts Eye and Ear Infirmary and Harvard Medical School Boston, 02114, Boston, MA, USA  |4 aut 
700 1 |a Kujawa  |D Sharon  |u Department of Otology and Laryngology Massachusetts Eye and Ear Infirmary and Harvard Medical School Boston, 02114, Boston, MA, USA  |4 aut 
700 1 |a Mescher  |D Mark  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
700 1 |a Fiering  |D Jason  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
700 1 |a Sewell  |D William  |u Department of Otology and Laryngology Massachusetts Eye and Ear Infirmary and Harvard Medical School Boston, 02114, Boston, MA, USA  |4 aut 
700 1 |a Borenstein  |D Jeffrey  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
773 0 |t Biomedical Microdevices  |d Springer US; http://www.springer-ny.com  |g 17/2(2015-04-01), 1-16  |x 1387-2176  |q 17:2<1  |1 2015  |2 17  |o 10544 
856 4 0 |u https://doi.org/10.1007/s10544-014-9923-8  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s10544-014-9923-8  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tandon  |D Vishal  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kang  |D Woo Seok  |u Department of Otology and Laryngology Massachusetts Eye and Ear Infirmary and Harvard Medical School Boston, 02114, Boston, MA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Spencer  |D Abigail  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kim  |D Ernest  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Pararas  |D Erin  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a McKenna  |D Michael  |u Department of Otology and Laryngology Massachusetts Eye and Ear Infirmary and Harvard Medical School Boston, 02114, Boston, MA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kujawa  |D Sharon  |u Department of Otology and Laryngology Massachusetts Eye and Ear Infirmary and Harvard Medical School Boston, 02114, Boston, MA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Mescher  |D Mark  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Fiering  |D Jason  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Sewell  |D William  |u Department of Otology and Laryngology Massachusetts Eye and Ear Infirmary and Harvard Medical School Boston, 02114, Boston, MA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Borenstein  |D Jeffrey  |u Charles Stark Draper Laboratory, 02139, Cambridge, MA, England  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Biomedical Microdevices  |d Springer US; http://www.springer-ny.com  |g 17/2(2015-04-01), 1-16  |x 1387-2176  |q 17:2<1  |1 2015  |2 17  |o 10544