J Drug Target., 14(4):225-32, 2006.

Enhancement of antitumor effect of doxorubicin by its complexation with gamma-cyclodextrin in pegylated liposomes.

Arima H, Hagiwara Y, Hirayama F, Uekama K.

Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.

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.