LHRHa mediated ovarian tumor targeting of docetaxel-loaded liposomes

摘要

In this study, a synthetic nonapeptide similar to luteinizing hormone-releasing hormone (LHRHa), the ligand of an extracellular membrane receptor specific to ovarian tumor cells, was selected as targeting moiety and electrically adsorped to the negatively charged lipsomes composed of phospholipid and monocholesterolsuccinate. Docetaxel was chosen to be encapsulated into the liposomes and a high encapsulate efficiency (93.14%) and drug loading efficiency (20.49%) was achieved. In order to investigate the targeting efficiency of the drug delivery system, in vitro cell uptake was carried out and the result showed an increasing uptake of LHRHa aided liposomes than that of normal ones. The model of ovarian cancer xenograft were also established for investigating biodistribution of docetaxel (Doc), docetaxel liposomes (Doc-Lipo), and LHRHa mediated docetaxel-loaded liposomes (LHRHa-Doc-Lipo) in nude mice. 60 min after administration of LHRHa-Doc-Lipo; the concentration of docetaxel in the ovarian tumor was 1.36 times higher than that of Doc-Lipo and 4.28 times higher than that of Doc in ovarian tumor beating nude mice. LHRHa-Doc-Lipo decreased the concentration of docetaxel in liver and spleen by 57% and 34% respectively, as compared with Doc-Lipo.