Hepatocyte-targeted delivery using ph-sensitive liposomes loaded with lactosylnorcantharidin phospholipid complex: preparation, characterization, and therapeutic evaluation in vivo and in vitro.

Z Qiao-ling, Z Yi, G Min, Y Di-jia, Z Xiao-feng, L Yang, X Jing-yu, W Ying, G Zong-lin, X Kong-lang, Z Ai-jun, C Wei-liang, S Lin-sen, Z Xue-nong, Z Qiang

Index: Curr. Med. Chem. 19(33) , 5754-63, (2012)

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Abstract

Liposomes loaded with lactosyl-norcantharidin phospholipid complex (LPC) were prepared, in which soybean phosphatidylcholine was used to improve the liposolubility of lactosyl-norcantharidin (Lac-NCTD). The pH-sensitive LPC liposomes (pH-LPC-lips) were obtained by electrostatic adsorption of the carboxymethyl chitosan onto the surface of the liposomes. The in vitro drug release of pH-LPC-lips and LPC-lips was investigated in dissolution media with pH ranging from 1.0 to 8.0. The in vitro antitumor activity and cellular uptake of Lac-NCTD and its liposomes to HepG2 cells were studied. The pH-LPC-lips demonstrated strong cytotoxicity against the cells and easily permeated the cell membrane. The in vivo antitumor activities of Lac-NCTD and its liposomes were evaluated in mice bearing H22 liver tumors. The pH-LPC-lips displayed the best tumor inhibitory effect. The optical imaging results indicated that Cy7- labeled pH-LPC-lips showed excellent hepatocyte specificity in H22 tumor-bearing mice. Therefore, pH-LPC-lips can be regarded as liver-targeting agents that combine targeting and active releasing.