Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles

Christine Dufès, Jean-Marc Muller, William Couet, Jean-Christophe Olivier, I.F. Uchegbu, Andreas G. Schätzlein

Research output: Contribution to journalArticle

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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.
LanguageEnglish
Pages101-7
Number of pages94
JournalPharmaceutical Research
Volume21
Issue number1
DOIs
StatePublished - 2004

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Chitosan
Transferrin
Drug delivery
Doxorubicin
Pharmaceutical Preparations
Cytotoxicity
Dimethyl Suberimidate
Glucose
Flow cytometry
Confocal microscopy
Glucosamine
Heterografts
Confocal Microscopy
Liposomes
Tumors
Assays
Flow Cytometry
Ligands
Safety
Neoplasms

Keywords

  • doxorubicin
  • glucose niosomes
  • glycol chitosan
  • polymeric vesicles
  • transferrin

Cite this

Dufès, C., Muller, J-M., Couet, W., Olivier, J-C., Uchegbu, I. F., & Schätzlein, A. G. (2004). Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles. Pharmaceutical Research, 21(1), 101-7. DOI: 10.1023/B:PHAM.0000012156.65125.01
Dufès, Christine ; Muller, Jean-Marc ; Couet, William ; Olivier, Jean-Christophe ; Uchegbu, I.F. ; Schätzlein, Andreas G./ Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles. In: Pharmaceutical Research. 2004 ; Vol. 21, No. 1. pp. 101-7
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Dufès, C, Muller, J-M, Couet, W, Olivier, J-C, Uchegbu, IF & Schätzlein, AG 2004, 'Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles' Pharmaceutical Research, vol. 21, no. 1, pp. 101-7. DOI: 10.1023/B:PHAM.0000012156.65125.01

Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles. / Dufès, Christine; Muller, Jean-Marc; Couet, William; Olivier, Jean-Christophe; Uchegbu, I.F.; Schätzlein, Andreas G.

In: Pharmaceutical Research, Vol. 21, No. 1, 2004, p. 101-7.

Research output: Contribution to journalArticle

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Dufès C, Muller J-M, Couet W, Olivier J-C, Uchegbu IF, Schätzlein AG. Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles. Pharmaceutical Research. 2004;21(1):101-7. Available from, DOI: 10.1023/B:PHAM.0000012156.65125.01