title: A novel cationic liposome formulation for efficient gene delivery via a pulmonary route.
abstract: The clinical success of gene therapy for lung cancer is not only dependent on efficient gene carriers but also on a suitable delivery route. A pulmonary delivery route can directly deliver gene vectors to the lung which is more efficient than a systemic delivery route. For gene carriers, cationic liposomes have recently emerged as leading non-viral vectors in worldwide gene therapy clinical trials. However, cytotoxic effects or apoptosis are often observed which is mostly dependent on the cationic lipid used. Therefore, an efficient and safe cationic lipid, 6-lauroxyhexyl lysinate (LHLN), previously synthesized by our group was first used to prepare cationic liposomes. Physicochemical and biological properties of LHLN-liposomes were investigated. LHLN-liposome/DNA complexes showed positive surface charge, spherical morphology, a relatively narrow particle size distribution and strong DNA binding capability. Compared with Lipofectamine2000, the new cationic liposome formulation using LHLN exhibited not only lower cytotoxicity (P < 0.05) but also similar transfection efficiency in A549 and HepG2 lung cancer cells for in vitro tests. When administered by intratracheal instillation into rat lungs for in vivo evaluation, LHLN-liposome/DNA complexes exhibited higher pulmonary gene transfection efficiency than Lipofectamine2000/DNA complexes (P < 0.05). These results suggested that LHLN-liposomes may have great potential for efficient pulmonary gene delivery.
authors.affiliation: School of Pharmaceutical Science, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Donghua
authors.initials: D
authors.lastname: Liu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Sun
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002412:Cations / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D055598:Chemical Phenomena / Q000187:drug effects; D004247:DNA / Q000097:blood; D003850:Deoxyribonuclease I / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007848:Laurates / Q000737:chemistry* / Q000633:toxicity; D008081:Liposomes / Q000097:blood / Q000737:chemistry* / Q000648:ultrastructure; D008168:Lung / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection
chemical_list: C557632:6-lauroxyhexyl lysinate; D002412:Cations; D007848:Laurates; D008081:Liposomes; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA; D003850:Deoxyribonuclease I; D008239:Lysine