Adequately-sized nanocarriers allow sustained targeted drug delivery to neointimal lesions in rat arteries
Adequately-sized nanocarriers allow sustained targeted drug delivery to neointimal lesions in rat arteries
复制标题
足够大小的纳米载体可以将靶向药物持续递送至大鼠动脉的新内膜病变处
DOI：
10.1021/acs.molpharmaceut.6b00219
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发表时间：
2016
影响因子：
4.9
通讯作者：
T. Watanabe
中科院分区：
文献类型：
--
作者：
R. Taniguchi;Y. Miura;H. Koyama;T. Chida;Y. Anraku;A. Kishimura;K. Shigematsu;K. Kataoka;T. Watanabe
在动脉粥样硬化病变中，抵抗血流的内皮屏障可能受损，导致细胞外基质（ECM）和下面的内膜细胞暴露。理论上，这允许循环中足够大小的纳米载体血管内浸润到内膜病变中。我们试图用诱导新生内膜的大鼠颈动脉来评估这种可能性。Cy 5-标记的聚乙二醇共轭聚离子复合物（PIC）胶束和囊泡，直径为40，100，或200 nm（PIC-40，PIC-100，和PIC-200，分别）静脉内给药后，大鼠颈动脉损伤使用球囊导管。体内成像证实了PIC-40在诱导的新生内膜中的高积累和长时间保留，而PIC-100和PIC-200的积累是有限的，表明纳米载体的大小是有效递送的关键因素。此外，表柔比星掺入聚合物胶束的直径类似的PIC-40显示出显着的疗效与诱导新生内膜的大鼠，在病变的大小和细胞数量。通过适当控制纳米载体的尺寸，证明了对预先存在的新生内膜病变的特异性和有效的药物递送。我们认为这种基于纳米载体的药物递送系统可用于治疗动脉粥样硬化。
In atherosclerotic lesions, the endothelial barrier against the bloodstream can become compromised, resulting in the exposure of the extracellular matrix (ECM) and intimal cells beneath. In theory, this allows adequately sized nanocarriers in circulation to infiltrate into the intimal lesion intravascularly. We sought to evaluate this possibility using rat carotid arteries with induced neointima. Cy5-labeled polyethylene glycol-conjugated polyion complex (PIC) micelles and vesicles, with diameters of 40, 100, or 200 nm (PICs-40, PICs-100, and PICs-200, respectively) were intravenously administered to rats after injury to the carotid artery using a balloon catheter. High accumulation and long retention of PICs-40 in the induced neointima was confirmed byin vivoimaging, while the accumulation of PICs-100 and PICs-200 was limited, indicating that the size of nanocarriers is a crucial factor for efficient delivery. Furthermore, epirubicin-incorporated polymeric micelles with a diameter similar to that of PICs-40 showed significant curative effects in rats with induced neointima, in terms of lesion size and cell number. Specific and effective drug delivery to pre-existing neointimal lesions was demonstrated with adequate size control of the nanocarriers. We consider that this nanocarrier-based drug delivery system could be utilized for the treatment of atherosclerosis.