Enhanced activity of streptomycin and chloramphenicol against intracellular Escherichia coli in the J774 macrophage cell line mediated by liposome delivery
Enhanced activity of streptomycin and chloramphenicol against intracellular Escherichia coli in the J774 macrophage cell line mediated by liposome delivery
复制标题
脂质体递送介导的链霉素和氯霉素对 J774 巨噬细胞系中细胞内大肠杆菌的增强活性
DOI：
10.1128/aac.24.5.742
复制
发表时间：
1983
影响因子：
4.9
通讯作者：
R. Richards
中科院分区：
文献类型：
--
作者：
M. Stevenson;A. Baillie;R. Richards
用乙醚注射法制备了卵磷脂酰胆碱的中性或阴离子大单层囊泡，包封链霉素和氯霉素。在一种简单的试管稀释法中，这两种脂质体形式的抗生素对大肠杆菌都没有活性。比较了游离型和脂质体两种抗生素对J774.2小鼠巨噬细胞内大肠杆菌的抑制作用。两种抗生素在中性脂质体中的表观抗菌活性提高了10倍以上，氯霉素在含有磷脂酰丝氨酸的阴离子脂质体中的抗菌活性也提高了10倍以上。在这一体外体系中，含有磷脂酸的阴离子脂质体对任何一种抗生素的载药量都远低于中性脂质体。细胞与含有抗生素或羧基荧光素的脂质体在4℃孵育可抑制细胞内的抗菌活性和细胞相关的荧光。脂质体抗生素的高细胞内活性与其被巨噬细胞吞噬、随后细胞内脂质体降解和抗生素释放相一致。脂质体修饰细胞摄取和抗生素在细胞内的分布可以用来延长现有的和新的药物对抗网状内皮系统细胞内感染的活性。
Streptomycin and chloramphenicol were entrapped within large neutral or anionic unilamellar vesicles of egg phosphatidylcholine prepared by an ether injection method. Both antibiotics in liposomal form were inactive against Escherichia coli in a simple tube dilution assay. A comparison was made of the activities of the free and liposomal forms of the antibiotics against E. coli located within the macrophages of the J774.2 murine cell line. The apparent intracellular antibacterial activity of both antibiotics was increased more than 10-fold by entrapment in neutral liposomes and in the case of chloramphenicol in anionic liposomes containing phosphatidylserine. Anionic liposomes containing phosphatidic acid were much less effective carriers than neutral liposomes for either antibiotic in this in vitro system. Incubation at 4 degrees C of cells with liposomes containing antibiotic or carboxyfluorescein inhibited intracellular antibacterial activity and cell-associated fluorescence. The high intracellular activity of the liposomal antibiotics is consistent with their phagocytic uptake by the macrophages followed by intracellular liposomal degradation and antibiotic release. Liposomal modification of cellular uptake and intracellular distribution of antibiotics may be used to extend the activity of existing and new agents against intracellular infection of the reticuloendothelial system.
影响因子：
56.9
作者：
GILOH, H;SEDAT, JW
通讯作者：
SEDAT, JW