EFFECT OF VESICLE SIZE ON THE CLEARANCE, DISTRIBUTION, AND TUMOR UPTAKE OF TEMPERATURE-SENSITIVE LIPOSOMES
EFFECT OF VESICLE SIZE ON THE CLEARANCE, DISTRIBUTION, AND TUMOR UPTAKE OF TEMPERATURE-SENSITIVE LIPOSOMES
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DOI：
10.1089/cdd.1986.3.223
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发表时间：
1986-09-01
期刊：
影响因子：
--
通讯作者：
BARK, GA
中科院分区：
文献类型：
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作者：
MAGIN, RL;HUNTER, JM;BARK, GA
测定了含有抗癌药物胞嘧啶[~3H]-1-β-D-阿糖胞苷(Ara-C)或[~3H]-甲氨蝶呤(MTX)的温敏性脂质体的血药清除率、组织分布和肿瘤摄取。用反相蒸发法制备由二棕榈酰磷脂酰胆碱和二棕榈酰磷脂酰甘油(重量比为4：1)组成的大分子单层脂质体，通过孔径分别为0.4、0.2、0.1、0.0 8和0.0 5μm的聚碳酸酯薄膜依次挤出，经尾静脉注射于B6D2F1小鼠双后足种植实体瘤(M5076卵巢癌)。在局部热疗(42℃，60分钟)过程中和之后，研究药物释放、器官分布和肿瘤摄取。与未加热的对照相比，局部热疗增加了脂质体在受热实体瘤中的相对载药量。清除性研究表明，脂质体的血清除量与脂质体的大小成反比。然而，减小脂质体大小对肿瘤摄取没有显著影响。此外，在所研究的脂质体大小范围内，大多数脂质体包裹的药物存在于肝、脾和肾中，而不是在加热的肿瘤中。
The blood clearance, tissue distribution, and tumor uptake of temperaturesensitive liposomes containing the anticancer drug cytosine [3H]-1-β-D-arabinofuranoside (Ara-C) or [3H]-methotrexate (MTX) were measured. Large unilamellar liposomes composed of a mixture of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol (4:1 by weight) were formed by reverse-phase evaporation and sequentially extruded through polycarbonate membranes with pore sizes of 0.4, 0.2, 0.1, 0.08, and 0.05 μm. The liposomes were injected intravenously via the tail vein into B6D2F1 mice containing solid tumors (M5076 ovarian carcinoma) implanted in both hind feet. Drug release, organ distribution, and tumor uptake were studied during and following local hyperthermia treatments (42°C, 60 minutes). Local hyperthermia increased the relative amount of liposome encapsulated drug delivered to a heated solid tumor compared with the unheated control. The clearance studies showed that liposome blood clearance was inversely proportional to liposome size. However, tumor uptake was not significantly affected by reducing liposome size. In addition, for the range of liposome sizes studied, the majority of the liposome encapsulated drug was found in the liver, spleen, and kidney; not in the heated tumor.