Prolonged circulation and increased tumor accumulation of liposomal vincristine in a mouse model of rhabdomyosarcoma

Nanomedicine (Lond). 2017 May;12(10):1135-1151. doi: 10.2217/nnm-2017-0430. Epub 2017 Apr 27.

Abstract

Aim: Our goal was to improve vincristine (VCR) based rhabdomyosarcoma (RMS) therapy by encapsulating the drug into liposomes. A targeting strategy was attempted to enhance tumor accumulation.

Materials & methods: VCR was loaded in control and peptide-decorated liposomes via an active method. The interaction of an RMS-specific peptide with the presumed target furin and the cellular uptake of both liposomal groups were studied in vitro. Pharmacokinetics and biodistribution of VCR-containing liposomes were assessed in an RMS xenograft mouse model.

Results: Liposomes ensured high VCR concentration in plasma and in the tumor. Peptide-decorated liposomes showed modest uptake in RMS cells.

Conclusion: The investigated peptide-modified liposomal formulation may not be optimal for furin-mediated RMS targeting. Nevertheless, VCR-loaded liposomes could serve as a delivery platform for experimental RMS.

Keywords: biodistribution; furin; liposomes; peptide; pharmacokinetic; rhabdomyosarcoma; targeting; vincristine.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / blood
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Cell Line, Tumor
  • Disease Models, Animal
  • Furin / metabolism
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Mice
  • Mice, Inbred NOD
  • Peptides / chemistry
  • Peptides / metabolism
  • Rhabdomyosarcoma / drug therapy*
  • Rhabdomyosarcoma / metabolism
  • Tissue Distribution
  • Vincristine / administration & dosage*
  • Vincristine / blood
  • Vincristine / pharmacokinetics

Substances

  • Antineoplastic Agents, Phytogenic
  • Liposomes
  • Peptides
  • Vincristine
  • Furin