Enhancement of antitumor effect of doxorubicin by its complexation with gamma-cyclodextrin in pegylated liposomes.
In the present study, we examined tissue distribution and the antitumor effect of doxorubicin (DOX) after intravenous injection of the pegylated liposomes entrapping the DOX complex with gamma-cyclodextrin (gamma-CyD) (complex-in-liposome) in BALB/c mice bearing colon-26 tumor cells, compared with those of DOX solution, pegylated liposomes entrapping DOX alone (DOX-in-liposome), pegylated liposomes entrapping gamma-CyD (CyD-in-liposome) and the binary system of DOX-in-liposome and CyD-in-liposome. When injected to the mice, complex-in-liposome provided the high DOX levels in plasma and solid tumors, compared with the other preparations. Reflecting the result, complex-in-liposome elicited the retardation of tumor growth and the improvement of survival rate without suppression of increase in the body weight of mice. These results suggest the potential use of pegylated liposomes entrapping the DOX complex with gamma-CyD for a promising carrier for improvement of antitumor effects of DOX.
Arima
Hidetoshi
H
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Hagiwara
Yoshiyuki
Y
Hirayama
Fumitoshi
F
Uekama
Kaneto
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D014018:Tissue Distribution; D016896:Treatment Outcome; D047408:gamma-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D047408:gamma-Cyclodextrins; D011092:Polyethylene Glycols; D004317:Doxorubicin