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

Author:

Roveri Maurizio123,Pfohl Alice123,Jaaks Patricia12,Alijaj Nagjie12,Leroux Jean-Christophe3,Luciani Paola34,Bernasconi Michele12

Affiliation:

1. Experimental Infectious Diseases & Cancer Research, University Children’s Hospital Zurich, 8008 Zurich, Switzerland

2. Children's Research Center, University Children’s Hospital Zurich, 8032 Zurich, Switzerland

3. Department of Chemistry & Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland

4. Department of Pharmaceutical Technology, Institute of Pharmacy, Friedrich Schiller University, 07743 Jena, Germany

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.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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