ABSTRACT
I. Scope of Chapter ....................................................................................................... 173
II. Drug Substance ......................................................................................................... 174 A. Clinical Use ......................................................................................................... 174 B. Mechanism of Action ......................................................................................... 174 C. Structure and Physical Chemistry ...................................................................... 174
HI. Liposome Formulation Methods ............................................................................... 174 A. Bilayer Entrapment Strategies ............................................................................ 174 B. pH-Mediated Drug Entrapment .......................................................................... 175 C. Steric Stabilization and Ammonium Gradient-Mediated
Drug Entrapment ................................................................................................. 176
IV. Pharmacokinetics ....................................................................................................... 177
V. Preclinical Toxicology .............................................................................................. 178
VI. In Vitro Tumor Models ............................................................................................. 179
VII. In Vivo Tumor Models .............................................................................................. 180 A. P388 Lymphocytic Leukemia ............................................................................. 180 B. Ll210 Leukemia ................................................................................................. 181 C. C26 Colon Carcinoma ........................................................................................ 182 D. MC2 Mammary Carcinoma ................................................................................ 182
VIII. Conclusions and Perspectives ................................................................................... 182
References ........................................................................................................................... 184
The concept and history of both conventional and long circulating Stealth®* liposomes have been reviewed in depth elsewhere in this book, so the focus here is to provide a complete review of the published literature on liposomal-encapsulated vincristine. The ultimate goal of formulating vincristine into liposomes is to make a significant improvement in clinical anticancer therapy. Therefore, this chapter will first summarize the action and pharmacology of vincristine, and then describe strategies that have been employed for formulating liposome-entrapped vincristine. The properties of these formulations will be detailed, and then the activity of these preparations will be compared in animal pharmacokinetics, toxicology, and tumor models.
