Alving C R, Steck E A, Chapman W L, Waits V B, Hendricks L D, Swartz G M, Hanson W L
Proc Natl Acad Sci U S A. 1978 Jun;75(6):2959-63. doi: 10.1073/pnas.75.6.2959.
Liposomes containing antimonial compounds trapped in the aqueous phase were tested in the treatment of experimental leishmaniasis. The rationale of this approach was based on the hypothesis that the liposomes and the parasite are taken up by the same cell, the reticuloendothelial cell, and we present electron microscopic evidence that supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When two antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to either of the free (unencapsulated) drugs. After infection, if untreated, all of the hamsters eventually would die from the disease. Liposome-encapsulated meglumine antimoniate was about 330-640 times more effective in causing a drop in the death rate than was the free antimonial. The efficacy of treatment was influenced by the lipid composition and charge of the liposomes. For example, positively charged liposomes containing egg phosphatidylcholine were much less effective than negatively charged ones. In contrast, positively and negatively charged sphingomyelin liposomes were equally effective. Liposomes containing phosphatidylserine (which were negatively charged, but also had a much higher charge density) were among the less-effective preparations. Among those tested, the most consistently efficacious liposomes contained highly saturated long-chain phospholipids (eg., dipalmitoyl phosphatidylcholine), cholesterol, and a negative charge. We conclude that liposomes may be useful as carriers of drugs to treat infectious diseases involving the reticuloendothelial system. The toxicities of antimony are very similar to those of arsenic. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis.
对包裹于水相中的含锑化合物脂质体进行了治疗实验性利什曼病的测试。该方法的理论依据基于这样一种假设，即脂质体和寄生虫会被同一个细胞——网状内皮细胞摄取，并且我们提供了支持这一假设的电子显微镜证据。通过测定肝脏印片上的寄生虫总数来量化利什曼病的抑制情况。当两种锑剂，葡甲胺锑酸盐和葡萄糖酸锑钠，被包裹在脂质体内时，它们各自的活性比游离（未包裹）药物中的任何一种都高出700倍以上。感染后，如果不进行治疗，所有仓鼠最终都会死于该病。脂质体包裹的葡甲胺锑酸盐在降低死亡率方面的效果比游离锑剂高出约330 - 640倍。治疗效果受脂质体的脂质组成和电荷影响。例如，含卵磷脂的带正电荷脂质体的效果远低于带负电荷的脂质体。相比之下，带正电荷和带负电荷的鞘磷脂脂质体效果相当。含磷脂酰丝氨酸的脂质体（带负电荷，但电荷密度也高得多）是效果较差的制剂之一。在测试的制剂中，最 consistently efficacious脂质体含有高度饱和的长链磷脂（如二棕榈酰磷脂酰胆碱）、胆固醇和负电荷。我们得出结论，脂质体可用作治疗涉及网状内皮系统的传染病的药物载体。锑的毒性与砷的毒性非常相似。包裹锑剂药物并减少有效治疗所需的剂量应能将急性心肌病和中毒性肾炎等全身毒性降至最低。
原文中“consistently efficacious”表述有误，推测可能是“consistently effective”，翻译时按推测修正后的内容翻译为“始终有效的” 。
