title: A Comparative Study of Drug Delivery Methods Targeted to the Mouse Inner Ear: Bullostomy Versus Transtympanic Injection.
abstract: We present two minimally invasive microsurgical techniques in rodents for specific drug delivery into the middle ear so that it may reach the inner ear. The first procedure consists of perforation of the tympanic bulla, termed bullostomy; the second one is a transtympanic injection. Both emulate human clinical intratympanic procedures. Chitosan-glycerophosphate (CGP) and Ringer´s Lactate buffer (RL) were used as biocompatible vehicles for local drug delivery. CGP is a nontoxic biodegradable polymer widely used in pharmaceutical applications. It is a viscous liquid at RT but it congeals to a semi solid phase at body temperature. RL is an isotonic solution used for intravenous administrations in humans. A small volume of this vehicle is precisely placed on the Round Window (RW) niche by means of a bullostomy. A transtympanic injection fills the middle ear and allows less control but broader access to the inner ear. The safety profiles of both techniques were studied and compared by using functional and morphological tests. Hearing was evaluated by registering the Auditory Brainstem Response (ABR) before and several times after microsurgery. The cytoarchitecture and preservation level of cochlear structures were studied by conventional histological techniques in paraformaldehyde-fixed and decalcified cochlear samples. In parallel, unfixed cochlear samples were taken and immediately frozen to analyze gene expression profiles of inflammatory markers by quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). Both procedures are suitable as drug delivery methods into the mouse middle ear, although transtympanic injection proved to be less invasive compared to bullostomy.
authors.affiliation: Instituto de Investigaciones Biomédicas (IIBm) Alberto Sols CSIC-UAM; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII); Instituto de Investigación Sanitaria La Paz (IdiPAZ); smurillo@iib.uam.es.
authors.forename: Silvia
authors.initials: S
authors.lastname: Murillo-Cuesta
authors.affiliation: Instituto de Investigaciones Biomédicas (IIBm) Alberto Sols CSIC-UAM.
authors.forename: Néstor
authors.initials: N
authors.lastname: Vallecillo
authors.affiliation: Instituto de Investigaciones Biomédicas (IIBm) Alberto Sols CSIC-UAM; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII); Facultad de Veterinaria, Universidad Complutense de Madrid.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cediel
authors.affiliation: Instituto de Investigaciones Biomédicas (IIBm) Alberto Sols CSIC-UAM; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII).
authors.forename: Adelaida M
authors.initials: AM
authors.lastname: Celaya
authors.affiliation: Instituto de Investigación Sanitaria La Paz (IdiPAZ); Departmento de Otorrino laringología, Hospital Universitario La Paz.
authors.forename: Luis
authors.initials: L
authors.lastname: Lassaletta
authors.affiliation: Instituto de Investigaciones Biomédicas (IIBm) Alberto Sols CSIC-UAM; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII); Instituto de Investigación Sanitaria La Paz (IdiPAZ).
authors.forename: Isabel
authors.initials: I
authors.lastname: Varela-Nieto
authors.affiliation: Instituto de Investigaciones Biomédicas (IIBm) Alberto Sols CSIC-UAM; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII); Facultad de Veterinaria, Universidad Complutense de Madrid.
authors.forename: Julio
authors.initials: J
authors.lastname: Contreras
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D016057:Evoked Potentials, Auditory, Brain Stem; D034381:Hearing Loss / Q000503:physiopathology / Q000628:therapy*; D007267:Injections; D051379:Mice; D008866:Microsurgery / Q000379:methods*; D019060:Minimally Invasive Surgical Procedures / Q000379:methods*; D013506:Otologic Surgical Procedures / Q000379:methods*; D012405:Round Window, Ear / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery*; D014432:Tympanic Membrane / Q000601:surgery*