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.

中文翻译：

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金纳米颗粒/ PKC Delta抑制剂肽杂种在大鼠体内的药代动力学，组织分布和安全性。

金纳米颗粒（GNP）对于药物输送极为有用，部分原因是它们具有高度可调的特性。但是，这种可变性使人们无法清楚地了解GNPs在药物递送中的药代动力学和毒性。在这里，我们介绍了我们的药物递送系统的清除，器官分布和急性毒性测试，该系统使用GNP和两个五肽来递送合理设计的肽类药物。我们发现，不论是否使用我们的治疗剂，GNP /肽杂合体都能从大鼠血液中快速清除，并且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。有或没有治疗肽的我们的GNP杂种的行为之间存在细微但可检测的差异。GNP /多肽杂化物在高达16倍治疗剂量的单次剂量下均未显示毒性证据，这通过一系列测试进行测量，包括血细胞组成，肝，肾和脾功能标志物水平，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，本文的结果可帮助指导类似GNP /肽药物递送系统的设计和使用。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，本文的结果可帮助指导类似GNP /肽药物递送系统的设计和使用。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，本文的结果可帮助指导类似GNP /肽药物递送系统的设计和使用。