Delivery of interleukin-18 gene to lung cancer cells using cationic emulsion.
Interleukin-18 (IL-18) is known to reduce melanoma lung metastases through various mechanisms. For the delivery of IL-18 gene into the lung, three different cationic emulsions as non-viral vectors were formulated using the same components of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-sn-glycero-3-trimethylammonium propane (DOTAP), and Tween 80 with distinct oils. By using the small particle size of physicochemically stable E3, the complex of E3/plasmid DNA encoding IL-18 (16:2.5, w/w) was transfected into lung cancer cells, and the amount of plasmid DNA transferred and the expression of both mRNA and protein for IL-18 were measured. When compared with Lipofectamine/DNA complexes, an E3/DNA complex was less toxic and induced a comparable cellular level of plasmid DNA and expression levels of both mRNA and protein for IL-18. After injecting E3/DNA complexes into mice, the distribution of plasmid DNA was the highest in the lung and the liver. Especially, the administration of E3/DNA complexes induced a more rapid and prolonged distribution of plasmid DNA encoding IL-18 into the lung than that of Lipofectamine/DNA ones. These data demonstrated that cationic emulsion E3 containing castor oil could be useful for a delivery of IL-18 gene targeting the lung as well as the liver without an additional homing device, implying a potential IL-18 delivery system for the treatment of lung cancer.
Kang
Hyun-Suk
HS
College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Jin
Shun-Ji
SJ
Myung
Chang-Seon
CS
Hwang
Sung-Joo
SJ
Park
Jeong-Sook
JS
D000818:Animals; D002368:Castor Oil / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018736:DNA Adducts / Q000008:administration & dosage / Q000378:metabolism; D004355:Drug Stability; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions / Q000008:administration & dosage* / Q000737:chemistry*; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D018014:Gene Transfer Techniques; D007275:Injections, Intravenous; D020382:Interleukin-18 / Q000008:administration & dosage* / Q000235:genetics*; D008055:Lipids / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D000069463:Olive Oil; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010938:Plant Oils / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011136:Polysorbates / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013024:Soybean Oil / Q000737:chemistry; D013552:Swine
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D018736:DNA Adducts; D045703:Emulsifying Agents; D004655:Emulsions; D005229:Fatty Acids, Monounsaturated; D020382:Interleukin-18; D008055:Lipids; C086724:Lipofectamine; D000069463:Olive Oil; D010714:Phosphatidylethanolamines; D010938:Plant Oils; D011136:Polysorbates; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D013024:Soybean Oil; D002368:Castor Oil; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane