title: Persistence, distribution, and impact of distinctly segmented microparticles on cochlear health following in vivo infusion.
abstract: Delivery of pharmaceuticals to the cochleae of patients with auditory dysfunction could potentially have many benefits from enhancing auditory nerve survival to protecting remaining sensory cells and their neuronal connections. Treatment would require platforms to enable drug delivery directly to the cochlea and increase the potential efficacy of intervention. Cochlear implant recipients are a specific patient subset that could benefit from local drug delivery as more candidates have residual hearing; and since residual hearing directly contributes to post-implantation hearing outcomes, it requires protection from implant insertion-induced trauma. This study assessed the feasibility of utilizing microparticles for drug delivery into cochlear fluids, testing persistence, distribution, biocompatibility, and drug release characteristics. To allow for delivery of multiple therapeutics, particles were composed of two distinct compartments; one containing polylactide-co-glycolide (PLGA), and one composed of acetal-modified dextran and PLGA. Following in vivo infusion, image analysis revealed microparticle persistence in the cochlea for at least 7 days post-infusion, primarily in the first and second turns. The majority of subjects maintained or had only slight elevation in auditory brainstem response thresholds at 7 days post-infusion compared to pre-infusion baselines. There was only minor to limited loss of cochlear hair cells and negligible immune response based on CD45+ immunolabling. When Piribedil-loaded microparticles were infused, Piribedil was detectable within the cochlear fluids at 7 days post-infusion. These results indicate that segmented microparticles are relatively inert, can persist, release their contents, and be functionally and biologically compatible with cochlear function and therefore are promising vehicles for cochlear drug delivery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1510-1522, 2016.
authors: Department of Biomedical Engineering, University of Michigan, Ann Arbor, 48109.|Kresge Hearing Research Institute, University of Michigan, Ann Arbor, 48109.
authors: Astin M
authors: AM
authors: Ross
authors: Department of Biomedical Engineering, University of Michigan, Ann Arbor, 48109.|Biointerfaces Institute, University of Michigan, Ann Arbor, 48109.
authors: Sahar
authors: S
authors: Rahmani
authors: Kresge Hearing Research Institute, University of Michigan, Ann Arbor, 48109.
authors: Diane M
authors: DM
authors: Prieskorn
authors: Biointerfaces Institute, University of Michigan, Ann Arbor, 48109.|Department of Biophysics, University of Michigan, Ann Arbor, 48109.
authors: Acacia F
authors: AF
authors: Dishman
authors: Kresge Hearing Research Institute, University of Michigan, Ann Arbor, 48109.
authors: Josef M
authors: JM
authors: Miller
authors: Department of Biomedical Engineering, University of Michigan, Ann Arbor, 48109.|Biointerfaces Institute, University of Michigan, Ann Arbor, 48109.|Department of Chemical Engineering, University of Michigan, Ann Arbor, 48109.
authors: Joerg
authors: J
authors: Lahann
authors: Kresge Hearing Research Institute, University of Michigan, Ann Arbor, 48109.
authors: Richard A
authors: RA
authors: Altschuler
mesh_terms: D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects / Q000502:physiology*; D065546:Drug Liberation; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects; D007150:Immunohistochemistry; D008863:Microspheres; D010891:Piribedil / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D010891:Piribedil
keywords: biocompatibility; cochlear drug delivery; electrohydrodynamic co-jetting; segmented microparticle