Prolonged retention of doxorubicin in tumor cells by encapsulation of γ-cyclodextrin complex in pegylated liposomes

For further increase of retention of doxorubicin (DOX) in tumor cells, we prepared the pegylated liposomes entrapping the complex of DOX with gamma-cyclodextrin (gamma-CyD) (complex-in-liposome), and then examined the physicochemical properties and the in vitro cellular uptake/release, compared with those of pegylated liposomes entrapping DOX alone (DOX-in-liposome). The particle sizes of these liposomes were almost comparable, and the entrapment ratios of both DOX and gamma-CyD in liposomes were more than 90%. The release of DOX from liposomes in the fetal calf serum (FCS) was significantly inhibited by entrapment of gamma-CyD in the liposomes. The cellular uptake of DOX into Colon-26 cells, a mouse rectal carcinoma cell line, after incubation with these liposomes was almost equivalent. However, the cellular release of DOX from cells in the complex-in-liposome system was markedly slower than that in the DOX-in-liposome system. These results suggest the potential use of liposomes containing the DOX/gamma-CyD complex for high retention of DOX in tumor cells.