Characteristics and biodistribution of cationic liposomes and their DNA complexes
Characteristics and biodistribution of cationic liposomes and their DNA complexes
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DOI：
10.1016/s0168-3659(00)00293-5
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发表时间：
2000-10-03
影响因子：
10.8
通讯作者：
Kitagawa, T
中科院分区：
文献类型：
--
作者：
Ishiwata, H;Suzuki, N;Kitagawa, T
我们已经开发了一些新的脂质体制剂的基因转染。由作为阳离子脂质、磷脂和胆固醇的O，O ′-双十四酰基-N-（α-三甲基铵乙酰基）二乙醇胺氯化物（DC-6-14）组成的制剂在具有血清的培养细胞中和体内显示出有效的基因转染活性，即，小鼠腹腔注射。本研究以DC-6 - 14脂质体作为基因治疗的药物（基因）载体，对其理化性质和体内生物分布进行了研究。DC-6-14脂质体-DNA复合物通常被认为具有正表面电荷。然而，根据DNA与脂质体的比例，复合物的zeta电位变为负值。复合物的直径也依赖于DNA-脂质体的比例，并表现出最大值时，它们的表面电位是中性的。当静脉注射后测定复合物的生物分布时，带正电荷的复合物显示出立即的肺蓄积。另一方面，带负电荷的复合物未显示肺蓄积。这些结果表明，用DC-6-14脂质体制备的DNA-脂质体复合物的生物分布取决于它们的表面电荷。因此，DC-6-14脂质体的一些表面改性可以改善其DNA复合物的生物分布并因此改善其靶向性。(C)2000 Elsevier Science B. V.保留所有权利。
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. (C) 2000 Elsevier Science B.V. All rights reserved.