title: Local drug delivery with a self-contained, programmable, microfluidic system.
abstract: The development and optimization of many new drug therapies requires long-term local delivery with controlled, but variable dosage. Current methods for chronic drug delivery have limited utility because they either cannot deliver drugs locally to a specific organ or tissue, do not permit changes in delivery rate in situ, or cannot be used in clinical trials in an untethered, wearable configuration. Here, we describe a small, self-contained system for liquid-phase drug delivery. This system enables studies lasting several months and infusion rates can be programmed and modified remotely. A commercial miniature pump is integrated with microfabricated components to generate ultralow flow rates and stroke volumes. Solutions are delivered in pulses as small as 370 nL, with pulses delivered at any interval of 1 min or longer. A unique feature of the system is the ability to infuse and immediately withdraw liquid, resulting in zero net volume transfer while compounds are exchanged by mixing and diffusion with endogenous fluid. We present in vitro results demonstrating repeatability of the delivered pulse volume for nearly 3 months. Furthermore, we present in vivo results in an otology application, infusing into the cochlea of a guinea pig a glutamate receptor antagonist, which causes localized and reversible changes in auditory sensitivity.
authors.affiliation: Charles Stark Draper Laboratory, Cambridge, MA, USA. jfiering@draper.com
authors.forename: J
authors.initials: J
authors.lastname: Fiering
authors.forename: M J
authors.initials: MJ
authors.lastname: Mescher
authors.forename: E E
authors.initials: EE
authors.lastname: Leary Swan
authors.forename: M E
authors.initials: ME
authors.lastname: Holmboe
authors.forename: B A
authors.initials: BA
authors.lastname: Murphy
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Peppi
authors.forename: W F
authors.initials: WF
authors.lastname: Sewell
authors.forename: M J
authors.initials: MJ
authors.lastname: McKenna
authors.forename: S G
authors.initials: SG
authors.lastname: Kujawa
authors.forename: J T
authors.initials: JT
authors.lastname: Borenstein
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003051:Cochlea / Q000601:surgery; D004304:Dosage Forms; D016503:Drug Delivery Systems; D004581:Electronics; D004867:Equipment Design; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006168:Guinea Pigs; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods*; D008904:Miniaturization; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology*; D017470:Receptors, Glutamate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D023382:Toxicity Tests, Acute
chemical_list: D004304:Dosage Forms; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017470:Receptors, Glutamate; C056723:FG 9041