BIODISTRIBUTION OF PH-SENSITIVE IMMUNOLIPOSOMES
BIODISTRIBUTION OF PH-SENSITIVE IMMUNOLIPOSOMES
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DOI：
10.1016/0304-4165(86)90197-2
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发表时间：
1986-12-10
期刊：
影响因子：
--
通讯作者：
HUANG, L
中科院分区：
文献类型：
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作者：
CONNOR, J;NORLEY, N;HUANG, L
将由二油酰磷脂酰乙醇胺和油酸（pH敏感）或二油酰磷脂酰胆碱和油酸（pH不敏感）组成的脂质体注射到C3 H和Balb/c小鼠中，以确定脂质和含水量的组织分布。通过使用[3 H]胆甾烷基醚监测脂质组分，并通过使用包封的125 I-酪氨酰-菊粉监测含水量。注射到两种类型的小鼠中的pH不敏感脂质体从血流中迅速清除，随后主要在肝脏中蓄积，随后在脾脏中蓄积。脂质体表面存在单克隆抗体导致肝脏蓄积轻微加速，但通常与无抗体脂质体的特征相同。pH敏感性脂质体在注射后暴露于小鼠血浆时泄漏。然而，脂质组分显示出大量（例如，在C3 H小鼠中为50-70%），在肺中蓄积长达6小时，随后出现在肝脏和脾脏中。单克隆抗体的存在对组织分布特征没有影响。这些结果表明，pH敏感性脂质体，虽然作为水性药物递送剂无效，但作为将亲脂性药物递送至肺的手段可能是有效的。
Liposomes composed of either dioleoylphosphatidylethanolamine and oleic acid (pH-sensitive) or dioleoylphosphatidylcholine and oleic acid (pH-insensitive) were injected into C3H and Balb/c mice in order to determine the tissue distribution of both the lipid and the aqueous content. The lipid component was monitored by use of [3H]cholestanyl ether and the aqueous content was monitored by use of encapsulated 125I-tyraminyl-inulin. The pH-insensitive liposomes injected into both types of mice were rapidly cleared from the blood stream followed by accumulation primarily in the liver, followed by the spleen. The presence of a monoclonal antibody on the liposome surface caused a slight acceleration in liver accumulation, though generally gave the same profile as the antibody-free liposomes. pH-sensitive liposomes were leaky upon exposure to the mouse plasma following injection. The lipid component, though, displayed a large amount (e.g., 50-70% in C3H mice) of accumulation in the lung for up to 6 h, followed by a subsequent appearance in the liver and spleen. The presence of monoclonal antibody had no effect on the tissue distribution profile. These results indicate that the pH-sensitive liposomes, although ineffective as an aqueous drug delivery agent, may be effective as a means of delivering lipophilic drugs to the lung.