Department of Otolaryngology, University of Tampere Medical School, Tampere, Finland.
Otol Neurotol. 2012 Jun;33(4):666-73. doi: 10.1097/MAO.0b013e318254590e.
The goal of this study was to evaluate the impact of liposome nanocarrier size on the efficacy of its transport across the middle-inner ear barriers.
The dynamic distribution of liposome nanocarriers encapsulating gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (LPS+Gd-DOTA) of sizes 95, 130, and 240 nm were observed with a 4.7 T magnetic resonance machine after transtympanic injection in Wistar rats. Histology was performed with confocal microscopy using TRITC conjugated LPS+Gd-DOTA. The integrity of the LPS+Gd-DOTA after transportation was evaluated using cryo-transmission electron microscopy (Cryo-TEM).
Size-dependent transport of the LPS+Gd-DOTA across the middle-inner ear barriers was shown using magnetic resonance imaging, which indicated that the 95-nm nanocarrier showed the significantly highest transport percentage, that the 130-nm nanocarrier showed moderate transport, and that the 240 nm nanocarrier showed the lowest transport. Histologic examinations showed that the LPS+Gd-DOTA were distributed in the epithelial cells of the utricle, capillaries of the spiral ligament, and the spiral ganglion cells. LPS+Gd-DOTA remained intact in the perilymph after transportation.
The nanocarrier delivery strategy used in this work could be effective in the development of novel inner ear treatments.
本研究旨在评估脂质体纳米载体大小对其穿过中耳-内耳屏障的传输效果的影响。
使用 4.7T 磁共振仪观察大小为 95、130 和 240nm 的脂质体纳米载体包封钆四氮杂环十二烷四乙酸（LPS+Gd-DOTA）的动态分布，经鼓室注射至 Wistar 大鼠后。使用 TRITC 标记的 LPS+Gd-DOTA 通过共聚焦显微镜进行组织学检查。使用冷冻透射电子显微镜（Cryo-TEM）评估 LPS+Gd-DOTA 在运输后的完整性。
磁共振成像显示 LPS+Gd-DOTA 穿过中耳-内耳屏障的传输具有尺寸依赖性，表明 95nm 纳米载体的传输百分比最高，130nm 纳米载体的传输效果适中，而 240nm 纳米载体的传输百分比最低。组织学检查显示，LPS+Gd-DOTA 分布于椭圆囊的上皮细胞、螺旋韧带的毛细血管和螺旋神经节细胞中。运输后，LPS+Gd-DOTA 仍保持在外淋巴液中完整。
本研究中使用的纳米载体传递策略可能对新型内耳治疗的发展有效。
