CHARACTERIZATION OF 5-FLUOROURACIL LOADED LIPOSOMES PREPARED BY REVERSE-PHASE EVAPORATION OR FREEZING-THAWING EXTRUSION METHODS - STUDY OF DRUG-RELEASE
CHARACTERIZATION OF 5-FLUOROURACIL LOADED LIPOSOMES PREPARED BY REVERSE-PHASE EVAPORATION OR FREEZING-THAWING EXTRUSION METHODS - STUDY OF DRUG-RELEASE
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DOI：
10.1016/0005-2736(93)90398-j
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发表时间：
1993-12-12
期刊：
影响因子：
--
通讯作者：
CHANTRES, JR
中科院分区：
文献类型：
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作者：
ELORZA, B;ELORZA, MA;CHANTRES, JR
以天然牛脑鞘磷脂（SM）和合成二硬脂酰磷脂酰胆碱（DSPC）为原料，采用冻融挤出法（FATVET）和逆相蒸发法（REV）制备了单层脂质体，并研究了其对抗癌药物5-氟尿嘧啶（5-FU）的包封作用。发现通过0.2 μ m孔径的聚碳酸酯膜从DSPC中获得的反相蒸发囊泡捕获的药物量大约是挤出脂质体（0.1 μ m孔径）的两倍;然而，这些制剂中的s-REV在囊泡尺寸上比FATVET更不均匀。发现从脂质体的体外药物释放速率依赖于双层组合物和用于制备囊泡的方法。获得的渗透系数P约为。10（-11）米/秒。结果表明，5-FU释放动力学控制的界面过程似乎依赖于药物的表面活性。此外，双层的物理状态决定了囊泡的保留能力。因此，脂质体组成的二硬脂酰磷脂酰胆碱，其酰基链在工作温度（37 ℃）下处于凝胶状态保留70%的封装的5-FU后1小时，而脂质体组成的天然牛脑鞘磷脂保留只有15%，在同一时期。
Entrapment of the anti-tumoral drug 5-fluorouracil (5-FU) in unilamellar liposomes prepared by freeze-thawing extrusion technique (FATVET) and the reverse-phase evaporation method (REV) from natural (bovine brain) sphingomyelin (SM) and synthetic distearoylphosphatidylcholine (DSPC) phospholipids was studied. Reverse-phase evaporation vesicles obtained from DSPC sized through polycarbonate membranes of 0.2 mu m pore size were found to entrap roughly double amounts of drug than did extruded liposomes (0.1 mu m pore size); however, s-REV in these preparations were more heterogenous in vesicle size than FATVET. The rate of in vitro drug release from the liposomes was found to be dependent of the bilayer composition and the method used to prepare the vesicles. The permeability coefficient P obtained was approx. 10(-11) m/s. The results suggest that 5-FU release is kinetically controlled by an interfacial process seemingly dependent on the surface activity of the drug. Also, the physical state of the bilayer determines the retention capacity of the vesicles. Thus, liposomes consisting of distearoylphosphatidylcholine whose acyl chains were in a gel state at the working temperature (37 degrees C) retained 70% of encapsulated 5-FU after 1 h, whereas liposomes composed of natural bovine brain sphingomyelin retained only 15% over the same period.