title: Ovarian tumor targeting of docetaxel-loaded liposomes mediated by luteinizing hormone-releasing hormone analogues. In vive distribution in nude mice.
abstract: Recent studies indicate that luteinizing hormone-releasing hormone (LHRH) analogues (LHRHa), like LHRH, are able to specifically bind to LHRH receptors which are highly expressed on the extracellular membrane of ovarian tumor cells. As a targeting moiety, LHRHa can mediate the ovarian tumor targeting of docetaxel-loaded liposomes. In our study, synthesized negatively charged cholesterol succinimide (CHS) was employed for the preparation of negatively charged docetaxel-loaded liposomes, with which the positively charged LHRHa is linked via electrostatic absorption. An HPLC-based assay for determination of docetaxel (CAS 114977-28-5, Doc) in vivo and the model of ovarian cancer xenograft were established to investigat the biodistribution of docetaxel, docetaxel liposomes (Doc-Lipo), and LHRHa mediated docetaxel-loaded liposomes (LHRHa-Doc-Lipo) in nude mice. Sixty minutes after administration of LHRHa-Doc-Lipo, the concentration of docetaxel in the ovarian tumor was 2.86 times that of Doc-Lipo and 9.02 times that of Doc in the nude mice bearing ovarian tumor. LHRHa-Doc-Lipo decreased the concentration of docetaxel in the liver and spleen by 57% and 34%, respectively, as compared with Doc-Lipo. Therefore, LHRHa-Doc-Lipo exhibits potentiality as an active targeting drug delivery system for chemotherapy of ovarian tumor.
authors.affiliation: Key Laboratory of Drug Targeting, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, The People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Qin
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Song
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
mesh_terms: D000042:Absorption; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002784:Cholesterol / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D000077143:Docetaxel; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D005612:Freeze Drying; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011355:Prodrugs; D015203:Reproducibility of Results; D013388:Succinimides / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014465:Ultrasonics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005079:Excipients; D008081:Liposomes; D011355:Prodrugs; D013388:Succinimides; D043823:Taxoids; C032620:succinimide; D000077143:Docetaxel; D007987:Gonadotropin-Releasing Hormone; D002784:Cholesterol