title: Label-Free Ferrocene-Loaded Nanocarrier Engineering for In Vivo Cochlear Drug Delivery and Imaging.
abstract: It is hypothesized that ferrocene (FC)-loaded nanocarriers (FC-NCs) are safe label-free contrast agents for cochlear biodistribution study by transmission electron microscopy (TEM). To test this hypothesis, after engineering, the poly(epsilon-caprolactone)/polyglycolide NCs are tested for stability with various types and ratios of sugar cryoprotectants during freeze-drying. Their physicochemical properties are characterized by UV-visible spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDS). The biodistribution of the FC-NCs in the cochlear tissue after intratympanic injection in guinea pigs is visualized by TEM. Auditory brainstem responses are measured before and after 4-day treatments. These FC-NCs have 153.4 ± 8.7 nm, 85.5 ± 11.2%, and -22.1 ± 1.1 mV as mean diameters, percent drug association efficiency, and zeta potential, respectively (n = 3). The incorporation of FC into the NCs is confirmed by Fourier transform infrared spectroscopy and SEM/EDS spectra. Lactose (3:1 ratio, v/v) is the most effective stabilizer after a 12-day study. The administered NCs are visible by TEM in the scala media cells of the cochlea. Based on auditory brainstem response data, FC-NCs do not adversely affect hearing. Considering the electrondense, radioactive, and magnetic properties of iron inside FC, FC-NCs are promising nanotemplate for future inner ear theranostics.
authors.affiliation: Hough Ear Institute, Oklahoma City, Oklahoma 73112.
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Youm
authors.affiliation: Pharmaceutical Technology & Regulatory Affairs "Maria Edvige Sangalli" Unit, Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milan 20133, Italy.
authors.forename: Umberto M
authors.initials: UM
authors.lastname: Musazzi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Saint-Louis University, St. Louis, Missouri 63110.
authors.forename: Michael Anne
authors.initials: MA
authors.lastname: Gratton
authors.affiliation: Department of Geosciences, University of Missouri-Kansas City, Kansas City, Missouri 64110.
authors.forename: James B
authors.initials: JB
authors.lastname: Murowchick
authors.affiliation: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, Missouri 64108. Electronic address: youanb@umkc.edu.
authors.forename: Bi-Botti C
authors.initials: BC
authors.lastname: Youan
mesh_terms: D000818:Animals; D057005:Bioengineering / Q000379:methods*; D003051:Cochlea / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000737:chemistry; D006168:Guinea Pigs; D000075163:Metallocenes; D008855:Microscopy, Electron, Scanning / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011897:Random Allocation; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
chemical_list: D004337:Drug Carriers; D005296:Ferrous Compounds; D000075163:Metallocenes; C004998:ferrocene
keywords: auditory brainstem response; cochlea; cryoprotectants; electron microscopy; ferrocene; freeze-dried nanocarriers; imaging