title: Lactoferrin modified doxorubicin-loaded procationic liposomes for the treatment of gliomas.
abstract: In this study, a brain-targeted chemotherapeutical delivery system, doxorubicin-loaded lactoferrin-modified procationic liposome (DOX-Lf-PCL) was developed, and its therapeutic effect for glioma was evaluated. The uptake profile of various DOX formulations in vitro by primary brain capillary endothelial cells (BCECs) and glioma cell C6 were studied by laser scanning confocal microscope and flow cytometry. An intracranial tumor model of rats was employed to evaluate the therapeutic effect of DOX-Lf-PCLs for glioma. Five groups of glioma-bearing rats (total n=50) were subjected to three cycles of 2.5mg/kg body weight of doxorubicin in different formulations or normal saline (N.S.) and analyzed for survival (median survival time, Kaplan-Meier). The results indicated that compared with the DOX solution or DOX-loaded conventional liposomes (DOX-Lips), DOX-PCLs and DOX-Lf-PCLs showed an improved performance in the uptake efficiency in BCECs and C6 cells. The DOX-Lf-PCLs can inhibit the growth of C6 more efficiently in vitro than other DOX formulations. The endocytosis involved in the DOX-Lf-PCLs uptake of C6 was mediated by both receptor- and absorption-mediated transcytosis. DOX-Lf-PCLs could significantly extend the survival time compared with the N.S. control and other DOX formulations. This study showed that the therapy with DOX-Lf-PCLs offers an effective therapeutic potential for gliomas.
authors.affiliation: Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, PR China.
authors.forename: Huali
authors.initials: H
authors.lastname: Chen
authors.forename: Yao
authors.initials: Y
authors.lastname: Qin
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007781:Lactoferrin / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin; D007781:Lactoferrin