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Cancer Chemotherapy and Pharmacology

, Volume 58, Issue 2, pp 245–255 | Cite as

Preferential extravasation and accumulation of liposomal vincristine in tumor comparing to normal tissue enhances antitumor activity

  • Siqing Shan
  • Clay Flowers
  • Cathy D. Peltz
  • Heather Sweet
  • Norbert Maurer
  • Eun-Joo Gina Kwon
  • Ave Krol
  • Fan Yuan
  • Mark W. DewhirstEmail author
Original Article

Abstract

To quantitatively evaluate the extravasation, accumulation and selectivity to tumor tissues of liposomal vincristine (LV), dorsal skin-fold window chambers on athymic mice with or without LX-1, a human small cell lung cancer, xenograft implants and fluorescent intravital microscopy imaging were used. In vitro studies show that minimal loss of fluorescence marker DiI from liposomes occurs after 4 days of inoculation in murine plasma, and the release profiles of DiI-LV and LV were essentially the same with approximately 40% of the encapsulated vincristine sulfate (VCR) released after 26 h. Significantly faster extravasation of DiI-LV from tumor vessels was shown compared to non-tumor tissue after single dose i.v. administration. The relative interstitial amounts at 60 min (RIA60) for tumor and non-tumor tissues were 0.837±0.314 and 0.012±0.091, respectively (P=0.01). DiI-LV accumulation was significantly higher in tumor than in normal tissue, which continued beyond 48 h. Both DiI-LV and LV showed significant antitumor effects in window chambers and in flank tumors, compared with controls and VLS alone. The preferential extravasation of DiI-LV from tumor vasculature as well as its differential retention in tumor tissue provides the basis for the enhancement in antitumor activity of LV over VCR.

Keywords

Vincristine Liposome Fluorescence microscopy Extravasation Drug release Dorsal skin fold window chamber LX-1 human small cell lung cancer 

Notes

Acknowledgements

The authors thank Ms. Dai Wang for the help in image analysis.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Siqing Shan
    • 1
  • Clay Flowers
    • 3
  • Cathy D. Peltz
    • 1
  • Heather Sweet
    • 3
  • Norbert Maurer
    • 3
  • Eun-Joo Gina Kwon
    • 3
  • Ave Krol
    • 2
  • Fan Yuan
    • 2
  • Mark W. Dewhirst
    • 1
    Email author
  1. 1.Department of Radiation OncologyDuke University Medical CenterDurhamUSA
  2. 2.Department of Biomedical EngineeringDuke UniversityDurhamUSA
  3. 3.Inex Pharmaceuticals CorporationBurnabyCanada

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