title: Characterization of highly stable liposomal and immunoliposomal formulations of vincristine and vinblastine.
abstract: OBJECTIVE
  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 (1/2) = 9.7 h) relative to vincristine (t (1/2) = 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.
authors.affiliation: Hermes Biosciences Inc, South San Francisco, CA 94080, USA.
authors.forename: Charles O
authors.initials: CO
authors.lastname: Noble
authors.forename: Zexiong
authors.initials: Z
authors.lastname: Guo
authors.forename: Mark E
authors.initials: ME
authors.lastname: Hayes
authors.forename: James D
authors.initials: JD
authors.lastname: Marks
authors.forename: John W
authors.initials: JW
authors.lastname: Park
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Benz
authors.forename: Dmitri B
authors.initials: DB
authors.lastname: Kirpotin
authors.forename: Daryl C
authors.initials: DC
authors.lastname: Drummond
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008081:Liposomes; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous; D014747:Vinblastine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014750:Vincristine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D014750:Vincristine; D014747:Vinblastine