title: Pulmonary gene delivery of hybrid vector, lipopolyplex containing N-lauroylsarcosine, via the systemic route.
abstract: We newly prepared lipopolyplexes containing N-lauroylsarcosine (LS) as a hybrid vector for pulmonary gene delivery via the systemic route. Lipopolyplexes were composed of polyethylenimine (PEI), N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethlylammonium chloride (DOTMA), LS, and plasmid DNA (pDNA). The particle size of lipopolyplex of PEI, DOTMA, and pDNA (lipopolyplex 2P-2D) was not largely changed by the addition of LS, although the addition of LS decreased the high zeta potential. Lipopolyplexes containing LS with low zeta potential showed little aggregation with erythrocytes and low cytotoxicity. In HepG2 cells, lipopolyplexes containing LS showed high transgene efficiency comparable to lipopolyplex 2P-2D. After intravenous injection of the complexes into mice, lipopolyplexes containing LS showed high transgene efficiency, comparable to lipopolyplex 2P-2D. In particular, lipopolyplexes containing LS showed extremely high transgene efficiency in the lung. As a result of the analysis to identify optimum formulations, we discovered that LS contributed to the high transgene efficiency in the lung as 76.7% of the contribution index. These results suggest that lipopolyplexes containing LS are safe and useful gene delivery vectors with lung directivity.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Reiko
authors.initials: R
authors.lastname: Kishikawa
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hamamoto
authors.forename: Hideto
authors.initials: H
authors.lastname: To
authors.forename: Takuro
authors.initials: T
authors.lastname: Niidome
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004903:Erythrocyte Aggregation / Q000187:drug effects; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000633:toxicity; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D010316:Particle Size; D010957:Plasmids; D011094:Polyethyleneimine / Q000737:chemistry / Q000633:toxicity; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000633:toxicity; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D014162:Transfection / Q000379:methods*
chemical_list: D008081:Liposomes; D000644:Quaternary Ammonium Compounds; C054005:N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium; C025231:sarkosyl; D011094:Polyethyleneimine; D008156:Luciferases; D012521:Sarcosine