Treatment of Large Solid Tumors in Mice with Daunomycin-Loaded Sterically Stabilized Liposomes

Abstract

Previous work on the effects of sterically stabilized liposomes on the growth of experimental solid tumors used protocols that began drug treatment when tumor volume was small (<0.01 mL). The goal of the present work was to compare the antitumor efficacy of daunomycin-loaded sterically stabilized liposomes versus free daunomycin in animals with large (>0.5 mL) experimental tumors. BALB/c nude mice were transplanted with 2.3 × 10⁶ 3T3 cells transfected with an activated HER2 gene. After 8 days, when mean tumor volume was 0.52 mL, mice were treated with intraperitoneal daunomycin-loaded polyethylene glycol-stabilized liposomes (daunomycin 6 mg/kg, including tracer [³H]daunomycin), free daunomycin (6 mg/kg), or vehicle. Both control and free daunomycin-treated mice survived an average of 15 days after tumor cell inoculation (and 7 days after treatment), while mice receiving daunomycin-loaded sterically stabilized liposomes survived for 32 days. Tumors were well vascularized and contained no necrotic centers. These studies demonstrate that sterically stabilized daunomycin-loaded liposomes are more effective in prolonging life span than an equivalent dose of free daunomycin even when therapy is initiated after the tumor volume reaches 2% of body weight.

Key Words:

• Chemotherapy
• Liposomes
• Sterically Stabilized Liposomes