title: A novel microperfusion system for the long-term local supply of drugs to the inner ear: implantation and function in the rat model.
abstract: Local therapy is practiced for middle and inner ear diseases but is usually restricted to cases of ear drum perforation or repeated invasive intratympanic drug application. Perfusion of drugs on the round window or through the scalae of animals using a pump system suggests that the chronic local drug treatment might also be feasible in humans. However, drug delivery systems that are currently on the market involve repeated reimplantation if they are to be used for long-term drug supply. A bone-anchored, totally implantable micro-drug delivery system (MDS) for patient-controlled drug supply has been developed [Lehner et al., 1997]. In this study, we show the first successful long-term in vivo test of the MDS micro-pump in rats. The process of implantation and first functional tests will be described. The biomaterial used to manufacture the delivery system did not cause any inflammation reaction in any of the 9 animals successfully implanted. After activation of the micro-pump, the drug reservoir and port was found to be fluid-tight. Bolus applications of tetrodotoxin (TTX) to the round window induced a transient decrease of evoked brainstem responses. In 2 animals which carried the MDS for more than 8 months the proper functioning of the pumping device was examined in a 2-3 week interval over a 3 month period. The MDS can be autoclaved even after long-term implantation and can then be reused for subsequent implantations. Designed for life-long implantation in humans, the demonstration of an effective long-term drug supply to the inner ear using the MDS provides an encouraging first step towards future long-term drug treatment of the inner ear in humans.
authors.affiliation: Department of Oto-Rhino-Laryngology, University Hospitals of the Saarland, Homburg/Saar, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Praetorius
authors.forename: A
authors.initials: A
authors.lastname: Limberger
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Lehner
authors.forename: B
authors.initials: B
authors.lastname: Schick
authors.forename: H P
authors.initials: HP
authors.lastname: Zenner
authors.forename: P
authors.initials: P
authors.lastname: Plinkert
authors.forename: M
authors.initials: M
authors.lastname: Knipper
mesh_terms: D000287:Administration, Topical; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D003051:Cochlea / Q000187:drug effects*; D004195:Disease Models, Animal; D004427:Ear Diseases / Q000188:drug therapy; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D015918:Infusion Pumps, Implantable; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D013995:Time
chemical_list: D000779:Anesthetics, Local; D013779:Tetrodotoxin