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To enhance the therapeutic efficacy as well as to reduce the side effect, we attempted to liposomalize 4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin (TOP-53), a novel and effective topoisomerase II inhibitor. More than 90% of TOP-53 was efficiently incorporated into the liposomes composed of dipalmitoylphosphatidylcholine and cholesterol by remote-loading method. Anti-tumor activity of liposomal TOP-53 against solid tumor was examined in vivo using colon26 NL-17 carcinoma model mice. Three doses of liposomal TOP-53 (12 mg/kg/dose) showed significant tumor growth suppression (97.5% reduction determined at day 25) and the increase in life span (33%) of tumor-bearing mice. Furthermore, one mouse out of 5 was completely cured after treatment. Since similar efficacy was observed in the free TOP-53 treated group, liposomalization does not contribute much to the enhancement of therapeutic efficacy. However, a slight but measurable damage at the injection site was observed when free TOP-53 was injected, and the damage was diminished by the liposomalization. Taken together, liposomalization reduces the side effect rather than enhancing the therapeutic efficacy when TOP-53 is used.

Potential Usage of Liposomal 4.BETA.-Aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin (TOP-53) for Cancer Chemotherapy.