Pharmacokinetics, tissue distribution and safety of gold nanoparticle/PKC Delta inhibitor peptide hybrid in rats

Hisato Konoeda, Hiromitsu Takizawa, Annette Gower, Michael Zhao, Oyedele A. Adeyi, Mingyao Liu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)341-354
Number of pages14
JournalNanotoxicology
Volume14
Issue number3
DOIs
StatePublished - Mar 15 2020
Externally publishedYes

Bibliographical note

Funding Information:
This work was funded by Canadian Institutes of Health Research Project Grant PJT148847, Medicine by Design?Canada First Research of Excellence Program, and Ontario Research Fund?Research Excellent RE-08-029.

Publisher Copyright:
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Drug delivery
  • GNP pharmacokinetics
  • GNP toxicity
  • GNP/peptide hybrid

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