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

Abstract

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.