Bakker-Woudenberg I A, ten Kate M T, Stearne-Cullen L E, Woodle M C
Department of Clinical Microbiology, Erasmus University, Rotterdam, Netherlands.
J Infect Dis. 1995 Apr;171(4):938-47. doi: 10.1093/infdis/171.4.938.
Polymer (PEG-PE)-coated liposomes exhibit prolonged circulation time in blood and substantial localization in Klebsiella pneumoniae-infected lung tissue in rats. Therefore, to determine the therapeutic effect, gentamicin and ceftazidime were entrapped in these liposomes and administered to rats experimentally infected with pneumonia: Relatively high and sustained concentrations of liposome-associated antibiotic in blood were observed. Compared with antibiotics alone, one dose of liposome-entrapped gentamicin or ceftazidime increased the therapeutic effect of the drugs, survival of rats, and bacterial killing in lungs. One dose of liposome-entrapped ceftazidime was as effective as a continuous 2-day infusion of nonentrapped ceftazidime. Since antibiotic-containing liposomes are stable during circulation and liposome-entrapped ceftazidime and gentamicin have low bactericidal activity in vitro, the superior therapeutic effect of the liposome-encapsulated antibiotics results from localization and subsequent degradation of liposomes and the resulting release of entrapped antibiotic at the infection site.
聚合物（聚乙二醇 - 磷脂酰乙醇胺）包被的脂质体在血液中的循环时间延长，并且在大鼠肺炎克雷伯菌感染的肺组织中有大量定位。因此，为了确定治疗效果，将庆大霉素和头孢他啶包封在这些脂质体中，并给予实验性感染肺炎的大鼠：观察到血液中脂质体相关抗生素的浓度相对较高且持续。与单独使用抗生素相比，一剂包封在脂质体中的庆大霉素或头孢他啶提高了药物的治疗效果、大鼠的存活率以及肺部细菌的清除率。一剂包封在脂质体中的头孢他啶与连续2天输注未包封的头孢他啶效果相同。由于含抗生素的脂质体在循环过程中稳定，且包封在脂质体中的头孢他啶和庆大霉素在体外杀菌活性较低，因此脂质体包裹抗生素的卓越治疗效果源于脂质体的定位和随后的降解，以及由此在感染部位释放包封的抗生素。
