Effect of hybridized liposome by novel modification with some polyethyleneglycol-lipids

This study is about hybridized liposome contained doxorubicin (Hy-LDOX) that has dual properties of stability in blood and incorporation in tumor cells. We used two kinds of polyethyleneglycol-lipids which are 1-monomethoxypolyethyleneglycol-2,3-distearoylglycerol (PEG-DSG) with an alkyl anchor and cholesterol-PEG (PEG-CHO) with a cholesterol anchor. Hy-LDOX was evaluated on antitumor activity (in vivo), DOX uptake into tumor cells, and DOX cytotoxicity (in vitro). Both tumor size and tumor weight in the Hy-LDOX group were decreased, compared with those in the control group. Hy-LDOX had increased DOX uptake into P388 leukemia cells, compared with the single PEG-DSG modified liposomes. Moreover, the IC(50) value, used as the index of the effect of cytotoxicity, significantly decreased in Hy-LDOX. We suggested that these results of DOX uptake and cytotoxicity contributed to PEG-CHO on liposomal membrane. The PEG modified liposome with only PEG-CHO cannot have a prolonged circulation time, but the Hy-LDOX which was modified with mixing PEG-lipids (PEG-DSG and PEG-CHO) showed stability in blood and incorporation in tumor cells. As the result of these experiments, Hy-LDOX were observed to be useful in terms of cell transition at target site, as shown by high DOX uptake into cell, and high cytotoxicity because PEG-CHO has good incorporated into tumor cell. Hence, it is expected that Hy-LDOX has novel functions.