Gold nanoparticles (GNPs) are extremely useful for drug delivery, due in part to their highly tunable nature. However, this variability has prevented a clear understanding of the pharmacokinetics and toxicity of GNPs for drug delivery. Here, we present the clearance, organ distribution and acute toxicity testing of our drug delivery system which uses GNPs and two penta-peptides, to deliver a rationally designed peptide drug. We found that with or without our therapeutic, the GNP/peptide hybrid cleared rapidly from the blood in rats and accumulated mostly in the liver and spleen, although it was also detectable in several other organs. There were subtle but detectable differences between the behavior of our GNP hybrids with or without the therapeutic peptide. The GNP/peptide hybrid showed no evidence of toxicity at single doses up to 16 times the therapeutic dose, as measured by a battery of tests including, blood cell makeup, levels of markers of liver, kidney and spleen function, organ mass indexes, and histology. These results underline the importance of testing the pharmacokinetics and toxicity of all GNP preparations, as even minor changes to the surface coatings of GNPs can influence their behavior. On the other hand, the results herein can help guide the design and use of similar GNP/peptide drug delivery systems.

译文

金纳米颗粒 (GNPs) 在药物输送方面非常有用,部分原因是它们高度可调。但是,这种可变性阻碍了对GNPs用于药物递送的药代动力学和毒性的清晰理解。在这里,我们介绍了我们的药物输送系统的清除,器官分布和急性毒性测试,该系统使用GNPs和两个五肽来输送合理设计的肽药物。我们发现,无论是否使用我们的治疗方法,GNP/肽杂合物都会从大鼠的血液中迅速清除,并主要在肝脏和脾脏中积累,尽管在其他几个器官中也可以检测到。在有或没有治疗肽的GNP杂种的行为之间存在细微但可检测的差异。通过一系列测试 (包括血细胞组成,肝,肾和脾功能标志物的水平,器官质量指数和组织学。)这些结果强调了测试所有GNP制剂的药代动力学和毒性的重要性,因为即使GNP表面涂层的微小变化也会影响其行为。另一方面,本文的结果可以帮助指导类似GNP/肽药物递送系统的设计和使用。

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