Characteristics and biodistribution of cationic liposomes and their DNA complexes.
We have developed some novel liposome formulations for gene transfection. The formulations consisting of O,O'-ditetradecanoyl-N-(alpha-trimethyl ammonio acetyl) diethanolamine chloride (DC-6-14) as a cationic lipid, phospholipid and cholesterol showed effective gene transfection activity in cultured cells with serum and in vivo, i.e., intraperitoneal injection in mice. In this report, the physicochemical characteristics and biodistribution of the liposomes containing DC-6-14 (DC-6-14 liposomes) as a drug (gene) carrier for gene therapy were investigated in vitro and in vivo. DC-6-14 liposome-DNA complexes were usually thought to have positive surface charge. However, depending on the ratio of DNA to liposomes, zeta-potential of the complexes became negative. The diameter of the complexes also depended on the DNA-liposome ratio, and showed a maximum when their surface potential was neutral. When biodistribution of the complexes was determined after intravenous injection, positively charged complexes showed an immediate lung accumulation. On the other hand, negatively charged complexes did not show lung accumulation. These results have suggested that biodistribution of the DNA-liposome complexes, prepared with DC-6-14 liposomes, depends on their surface charge. Therefore, some surface modification of DC-6-14 liposomes may improve the biodistribution and hence the targetability of their DNA complexes.
Ishiwata
H
H
Pharmaceutical Formulation Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center, 16-13 Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan. ishiw9fq@daiichipharm.co.jp
Suzuki
N
N
Ando
S
S
Kikuchi
H
H
Kitagawa
T
T
D000818:Animals; D001772:Blood Cell Count; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D004247:DNA