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Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles

Dufès, Christine and Muller, Jean-Marc and Couet, William and Olivier, Jean-Christophe and Uchegbu, I.F. and Schätzlein, Andreas G. (2004) Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles. Pharmaceutical Research, 21 (1). pp. 101-7. ISSN 0724-8741

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    Abstract

    The study reports the initial biological evaluation of targeted polymeric glycol chitosan vesicles as carrier systems for doxorubicin (Dox). Transferrin (Tf) was covalently bound to the Dox-loaded palmitoylated glycol chitosan (GCP) vesicles using dimethylsuberimidate (DMSI). For comparison, glucose targeted niosomes were prepared using N-palmitoyl glucosamine. Biological properties were studied using confocal microscopy, flow cytometry, and cytotoxicity assays as well as a mouse xenograft model. Tf vesicles were taken up rapidly with a plateau after 1-2 h and Dox reached the nucleus after 60-90 min. Uptake was not increased with the use of glucose ligands, but higher uptake and increased cytotoxicity were observed for Tf targeted as compared to GCP Dox alone. In the drug-resistant A2780AD cells and in A431 cells, the relative increase in activity was significantly higher for the Tf-GCP vesicles than would have been expected from the uptake studies. All vesicle formulations had a superior in vivo safety profile compared to the free drug. The in vitro advantage of targeted Tf vesicles did not translate into a therapeutic advantage in vivo. All vesicles reduced tumor size on day 2 but were overall less active than the free drug.

    Item type: Article
    ID code: 7826
    Keywords: doxorubicin, glucose niosomes, glycol chitosan, polymeric vesicles, transferrin, Pharmacy and materia medica
    Subjects: Medicine > Pharmacy and materia medica
    Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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      Depositing user: Strathprints Administrator
      Date Deposited: 03 Apr 2009 15:39
      Last modified: 24 Jul 2013 13:26
      URI: http://strathprints.strath.ac.uk/id/eprint/7826

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