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Characterization of highly stable liposomal and immunoliposomal formulations of vincristine and vinblastine

Cancer Chemotherapy and Pharmacology, ISSN: 0344-5704, Vol: 64, Issue: 4, Page: 741-751
2009
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Article Description

Purpose: Liposome and immunoliposome formulations of two vinca alkaloids, vincristine and vinblastine, were prepared using intraliposomal triethylammonium sucroseoctasulfate and examined for their ability to stabilize the drug for targeted drug delivery in vivo. Methods: The pharmacokinetics of both the encapsulated drug (vincristine or vinblastine) and liposomal carrier were examined in Sprague Dawley rats, and the in vivo drug release rates determined. Anti-HER2 immunoliposomal vincristine was prepared from a human anti-HER2/neu scFv and studied for targeted cytotoxic activity in cell culture, and antitumor efficacy in vivo. Results: Nanoliposome formulations of vincristine and vinblastine demonstrated similar pharmacokinetic profiles for the liposomal carrier, but increased clearance for liposome encapsulated vinblastine (t = 9.7 h) relative to vincristine (t = 18.5 h). Immunoliposome formulations of vincristine targeted to HER2 using an anti-HER2 scFv antibody fragment displayed a marked enhancement in cytotoxicity when compared to non-targeted liposomal vincristine control; 63- or 253-fold for BT474 and SKBR3 breast cancer cells, respectively. Target-specific activity was also demonstrated in HER2-overexpressing human tumor xenografts, where the HER2-targeted formulation was significantly more efficacious than either free vincristine or non-targeted liposomal vincristine. Conclusions: These results demonstrate that active targeting of solid tumors with liposomal formulations of vincristine is possible when the resulting immunoliposomes are sufficiently stabilized. © 2009 Springer-Verlag.

Bibliographic Details

Noble, Charles O; Guo, Zexiong; Hayes, Mark E; Marks, James D; Park, John W; Benz, Christopher C; Kirpotin, Dmitri B; Drummond, Daryl C

Springer Science and Business Media LLC

Medicine; Pharmacology, Toxicology and Pharmaceutics; Biochemistry, Genetics and Molecular Biology

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