title: Hepatocyte-targeted delivery using ph-sensitive liposomes loaded with lactosylnorcantharidin phospholipid complex: preparation, characterization, and therapeutic evaluation in vivo and in vitro.
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.
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutics, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Qiao-ling
authors.forename: Z
authors.initials: Z
authors.lastname: Yi
authors.forename: G
authors.initials: G
authors.lastname: Min
authors.forename: Y
authors.initials: Y
authors.lastname: Di-jia
authors.forename: Z
authors.initials: Z
authors.lastname: Xiao-feng
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: X
authors.initials: X
authors.lastname: Jing-yu
authors.forename: W
authors.initials: W
authors.lastname: Ying
authors.forename: G
authors.initials: G
authors.lastname: Zong-lin
authors.forename: X
authors.initials: X
authors.lastname: Kong-lang
authors.forename: Z
authors.initials: Z
authors.lastname: Ai-jun
authors.forename: C
authors.initials: C
authors.lastname: Wei-liang
authors.forename: S
authors.initials: S
authors.lastname: Lin-sen
authors.forename: Z
authors.initials: Z
authors.lastname: Xue-nong
authors.forename: Z
authors.initials: Z
authors.lastname: Qiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004187:Disaccharides / Q000737:chemistry; D016503:Drug Delivery Systems; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D010743:Phospholipids / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004187:Disaccharides; D008081:Liposomes; D010743:Phospholipids; C005608:lactobionic acid; C069741:norcantharidin