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用于体内耳蜗药物递送与成像的无标记负载二茂铁纳米载体工程

Label-Free Ferrocene-Loaded Nanocarrier Engineering for In Vivo Cochlear Drug Delivery and Imaging.

作者信息

Youm Ibrahima, Musazzi Umberto M, Gratton Michael Anne, Murowchick James B, Youan Bi-Botti C

机构信息

Hough Ear Institute, Oklahoma City, Oklahoma 73112.

Pharmaceutical Technology & Regulatory Affairs "Maria Edvige Sangalli" Unit, Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milan 20133, Italy.

出版信息

J Pharm Sci. 2016 Oct;105(10):3162-3171. doi: 10.1016/j.xphs.2016.04.012. Epub 2016 Jul 19.

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.

摘要

据推测,负载二茂铁(FC)的纳米载体(FC-NCs)是用于通过透射电子显微镜(TEM)进行耳蜗生物分布研究的安全无标记造影剂。为了验证这一假设,在进行工程设计后,对聚(ε-己内酯)/聚乙交酯纳米载体在冷冻干燥过程中与各种类型和比例的糖类冷冻保护剂的稳定性进行了测试。通过紫外可见光谱、动态光散射、傅里叶变换红外光谱以及扫描电子显微镜结合能量色散X射线光谱(SEM/EDS)对其理化性质进行了表征。通过TEM观察豚鼠鼓室内注射后FC-NCs在耳蜗组织中的生物分布。在4天治疗前后测量听觉脑干反应。这些FC-NCs的平均直径、药物结合效率百分比和zeta电位分别为153.4±8.7nm、85.5±11.2%和-22.1±1.1mV(n = 3)。傅里叶变换红外光谱和SEM/EDS光谱证实了FC掺入到纳米载体中。经过12天的研究,乳糖(3:1比例,v/v)是最有效的稳定剂。通过TEM可在耳蜗的中阶细胞中看到给药后的纳米载体。根据听觉脑干反应数据,FC-NCs不会对听力产生不利影响。考虑到FC中铁的电子致密、放射性和磁性特性,FC-NCs是未来内耳治疗诊断学中有前景的纳米模板。

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