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Hepatocyte-Targeted Delivery Using pH-Sensitive Liposomes Loaded with Lactosylnorcantharidin Phospholipid Complex: Preparation, Characterization, and Therapeutic Evaluation In Vivo and In Vitro

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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.
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Keywords: HepG2 cells; Hepatocyte-targeted delivery; cellular uptake; cytotoxicity; lactosyl-norcantharidin; lipsomes; near-infrared fluoressence; pH sensitive; phospholipid complex; release

Document Type: Research Article

Publication date: 2012-11-01

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