Prolonged Circulation and Increased Tumor Accumulation of Liposomal Vincristine in a Mouse Model of Rhabdomyosarcoma

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

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Acknowledgements

This work was supported by the Phospholipid Research Center, Heidelberg, Germany, the Swiss Cancer League, the Olga Mayenfisch Foundation, the Monika Anna Müller Grant and the Krebsliga Zurich. Lipoid GmbH is acknowledged for the endowment to the University of Jena (P Luciani). The authors wish to thank P Tiefenböck for the kind help with microscopy, D Mazunin for his help with the MALDI–TOF as well M Menzi for help and advice with the SPR.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.