Pharmacokinetics and efficacy of doxorubicin-loaded plant virus nanoparticles in preclinical models of cancer

Nanomedicine (Lond). 2017 Oct;12(20):2519-2532. doi: 10.2217/nnm-2016-0421. Epub 2017 Sep 27.

Abstract

Aim: To compare the pharmacokinetics and efficacy of doxorubicin containing plant virus nanoparticles (PVNs) with PEGylated liposomal doxorubicin (PLD) and small molecule doxorubicin in two mouse models of cancer.

Materials & methods: Studies were performed in A375 melanoma and intraperitoneal SKOV3ip1 ovarian cancer xenografts. The PVNs were administered in lower and more frequent doses in the ovarian model.

Results: The PVNs were more efficacious than PLD and small molecule doxorubicin in the ovarian cancer model, but not in the melanoma cancer model. The pharmacokinetics profiles of the PVNs showed fast plasma clearance, but more efficient tumor delivery as compared with other carrier-mediated agents.

Conclusion: PVNs administered at lower repeated doses provide both pharmacologic and efficacy advantages compared with PLD.

Keywords: efficacy; pharmacokinetics; plant virus nanoparticles.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / toxicity
  • Chemistry, Pharmaceutical / methods
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / toxicity
  • Drug Carriers / chemistry
  • Drug Liberation
  • Female
  • Humans
  • Kinetics
  • Mice
  • Mice, SCID
  • Microscopy, Electron, Transmission / methods
  • Mosaic Viruses / chemistry*
  • Nanoparticles / chemistry*
  • Ovarian Neoplasms / drug therapy*
  • Particle Size
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics
  • Polyethylene Glycols / toxicity
  • Surface Properties
  • Tissue Distribution
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin