title: Potential usage of liposomal 4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin (TOP-53) for cancer chemotherapy.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Shimizu
authors.forename: Miki
authors.initials: M
authors.lastname: Takada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Kenji
authors.initials: K
authors.lastname: Irimura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Baba
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D001808:Blood Vessels / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008081:Liposomes; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D016019:Survival Analysis; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008081:Liposomes; C099874:TOP 53; D059005:Topoisomerase II Inhibitors; D015060:1,2-Dipalmitoylphosphatidylcholine; D005047:Etoposide