Deĝim Zelihagül, Deĝim Tuncer, Bas Levent, Elmas Muammer
University of Gazi, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06330 Etiler, Ankara, Turkey.
J Biomed Mater Res. 2002 Aug;61(2):246-51. doi: 10.1002/jbm.10161.
It is difficult to treat intracellular infections because of the intrinsic resistance of the microorganism to most antibiotics. Moreover, these microorganisms can survive in phagocytic cells (macrophages and neutrophils). In this study, our aims were to encapsulate an antibiotic in liposomes, which will be phagocytized as well as the microorganisms in the phagocytic cell (because liposomes were prepared using lipids which have an antigenic activity and they can be phagocytized, thus, the active substance can be transferred into the cell), and to visualise with microscopy the phagocytic activity of macrophages and neutrophils to liposomes. MLV (multilamellar vesicles) fluorescein-labeled liposomes were prepared and incubated with isolated Kangal shepherd dog macrophages and neutrophils. The phagocytosis of liposomes by monocytes was visualized step by step under the microscope. Liposomes were also observed phagocytized after incubation with neutrophils. Enrofloxacin was chosen as a model drug. Neutrophils and macrophages were isolated from Kangal shepherd dogs and infected with Staphylococcus aureus, and their phagocytic activities (PA) and microbicidal activities (MA) were determined. PA and MA values were redetermined and compared when enrofloxacin formulations were used. Liposomal enrofloxacin was found to be more effective.
由于微生物对大多数抗生素具有内在抗性，因此治疗细胞内感染很困难。此外，这些微生物能够在吞噬细胞（巨噬细胞和中性粒细胞）中存活。在本研究中，我们的目的是将抗生素包裹在脂质体中，脂质体将与吞噬细胞中的微生物一样被吞噬（因为脂质体制备所用的脂质具有抗原活性，它们能够被吞噬，从而活性物质可被转运到细胞中），并通过显微镜观察巨噬细胞和中性粒细胞对脂质体的吞噬活性。制备了多层囊泡（MLV）荧光素标记的脂质体，并将其与分离出的坎高牧羊犬巨噬细胞和中性粒细胞一起孵育。在显微镜下逐步观察单核细胞对脂质体的吞噬作用。在与中性粒细胞孵育后也观察到脂质体被吞噬。选择恩诺沙星作为模型药物。从坎高牧羊犬中分离出中性粒细胞和巨噬细胞，并使其感染金黄色葡萄球菌，然后测定它们的吞噬活性（PA）和杀菌活性（MA）。当使用恩诺沙星制剂时，重新测定并比较PA和MA值。发现脂质体恩诺沙星更有效。
