期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 105, 期 10, 页码 3162-3171出版社
WILEY
DOI: 10.1016/j.xphs.2016.04.012
关键词
auditory brainstem response; cochlea; cryoprotectants; electron microscopy; ferrocene; freeze-dried nanocarriers; imaging
资金
- Saint Louis University (SLU) President's Research
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. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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