Straub S X, Garry R F, Magee W E
Infect Immun. 1974 Oct;10(4):783-92. doi: 10.1128/iai.10.4.783-792.1974.
Liposomes were prepared with phospholipids (sphingomyelin, lecithin, and phosphatidylethanolamine) in combination with cholesterol and charged lipids (dicetyl phosphate and stearylamine) and contained either poly(I):poly(C) or poly(I). Neutral and positively charged liposomes attached much better to L-929 cells in tissue culture than did negatively charged particles. Liposomes were toxic to L cells at relatively low concentrations, making the determination of antiviral activity induced by particles containing poly(I):poly(C) difficult to measure by the plaque reduction assay. When injected into mice, all of the liposomes containing poly(I):poly(C), except phosphatidylethanolamine liposomes, greatly potentiated and extended the serum interferon response of poly(I):poly(C). Lecithin and sphingomyelin liposomes given intravenously were ten times more effective than free poly(I):poly(C) in stimulating production of serum interferon. Sphingomyelin liposomes containing [(14)C]poly(I):poly(C) were 88% cleared from the bloodstream of mice by 3 min after intravenous injection. Most of the radioactivity (70%) was captured by the liver and remained there for at least 4 h. By 2 h, 7% of the radioactivity could be found in the spleen. Five percent of the radioactivity was found in the lungs at 30 min, with decreasing amounts thereafter. Small amounts of radioactivity were found in the muscle and kidneys. The spleen was shown to contain appreciable levels of interferon at 4 h, and low levels were found in the liver. Radioactivity accumulated slowly in the liver following an intraperitoneal injection of sphingomyelin liposomes containing [(14)C]poly(I):poly(C). By 4 h, 26% of the dose was recovered from the liver and 4.9% from the spleen, with small amounts in the lung, kidney, and omentum.
脂质体由磷脂（鞘磷脂、卵磷脂和磷脂酰乙醇胺）与胆固醇及带电脂质（磷酸二鲸蜡酯和硬脂胺）混合制备而成，其内部含有聚（I）:聚（C）或聚（I）。在组织培养中，中性和带正电荷的脂质体比带负电荷的颗粒更好地附着于L - 929细胞。脂质体在相对低的浓度下对L细胞有毒性，这使得通过蚀斑减少试验来测定含聚（I）:聚（C）颗粒诱导的抗病毒活性变得难以测量。当注射到小鼠体内时，除了磷脂酰乙醇胺脂质体之外，所有含聚（I）:聚（C）的脂质体都极大地增强并延长了聚（I）:聚（C）的血清干扰素反应。静脉注射的卵磷脂和鞘磷脂脂质体在刺激血清干扰素产生方面比游离的聚（I）:聚（C）有效十倍。含[（14）C]聚（I）:聚（C）的鞘磷脂脂质体在静脉注射后3分钟内从小鼠血液中清除了88%。大部分放射性（70%）被肝脏捕获并在那里停留至少4小时。到2小时时，在脾脏中可发现7%的放射性。在30分钟时，5%的放射性出现在肺部，此后含量逐渐减少。在肌肉和肾脏中发现少量放射性。在4小时时，脾脏显示含有相当水平的干扰素，而在肝脏中发现的水平较低。腹腔注射含[（14）C]聚（I）:聚（C）的鞘磷脂脂质体后，放射性在肝脏中缓慢积累。到4小时时，从肝脏中回收了26%的剂量，从脾脏中回收了4.9%，在肺、肾和网膜中有少量。
