Pharmacokinetics of peptide mediated delivery of anticancer drug ellipticine

PLoS One. 2012;7(8):e43684. doi: 10.1371/journal.pone.0043684. Epub 2012 Aug 31.

Abstract

The amino acid pairing peptide EAK16-II (EAK) has shown the ability to stabilize the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this study, we investigate pharmacokinetics of the formulation of EAK-EPT complexes in vivo. The developed formulation can achieve a sufficiently high drug concentration required in vivo animal models. The nanostructure and surface properties of EAK-EPT complexes or nanoparticle were characterized by transmission electron microscopy (TEM) and zeta potential measurements, respectively. 12 healthy male SD rats were divided into EPT group and EAK-EPT group randomly. Rats in EPT group were tail intravenously injected with the EPT (20 mg/kg); rats in EAK-EPT group were injected with EAK-EPT complexes (EPT's concentration is 20 mg/kg). EPT was extracted from rat plasma with dexamethasone sodium phosphate as internal standards (IS). The pharmacokinetic parameters were obtained using high pressure liquid chromatography (HPLC). Significant differences in main pharmacokinetic parameters between EPT and EAK-EPT complexes were observed, demonstrating that the complexation with EAK prolongs the residence time of the drug and enlarges the area under the concentration-time curve (AUC). This means that EAK can serve as a suitable carrier to increase the bioavailability of EPT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / pharmacokinetics*
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Ellipticines / pharmacokinetics*
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Nanostructures / chemistry
  • Peptides / chemistry
  • Peptides / metabolism*
  • Protein Conformation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Ellipticines
  • Peptides
  • ellipticine

Grants and funding

This project was supported by the Shanghai Committee of Science and Technology, China (Grant No. 10410711300). This research was financially supported by the Natural Sciences and Engineering Research Council of Canada, Canadian Foundation for Innovation and the Canada Research Chairs Program for one of the co-authors (PC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.