Effect of composition on the stability of liposomal irinotecan prepared by a pH gradient method
Effect of composition on the stability of liposomal irinotecan prepared by a pH gradient method
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DOI：
10.1263/jbb.95.405
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发表时间：
2003-04-01
影响因子：
2.8
通讯作者：
Chu, IM
中科院分区：
文献类型：
--
作者：
Chou, TH;Chen, SC;Chu, IM
通过pH梯度加载制备脂质体伊立替康。控制该过程的参数，包括载药时间，孵育温度，用于水合的缓冲液组合物，和DeltapH，进行了研究。检查了伊立替康在脂质体系统中的摄取对pH梯度大小的响应。当DeltapH的大小接近3.7时，药物摄取最大。同时考察了脂质体的处方对药物释放系统稳定性的影响。由具有高相变温度的脂质、L-α-二硬脂酰磷脂酰胆碱和氢化大豆磷脂酰胆碱组成的脂质体比由具有较低相变温度的脂质组成的脂质体更稳定。将二硬脂酰磷脂酰乙醇胺-聚（乙二醇）（2000）掺入脂质体有助于减小脂质体的尺寸。此外，发现通过在脂质体制剂中包括二肉豆蔻酰磷脂酰甘油或硫酸葡聚糖，药物在脂质体内的保留略有增强。
Liposomal irinotecan was prepared by pH gradient loading. The parameters that govern this process, including drug loading time, incubation temperature, buffer composition for hydration, and DeltapH, were studied. The uptake of irinotecan into liposomal systems in response to the magnitude of the pH gradient was examined. The drug uptake was maximum when the magnitude of DeltapH approached 3.7. The effect of the formulation of the liposomes on the stability of the drug delivery system was also studied. Liposomes composed of lipids with a high phase transition temperature, L-alpha-distearoyl-phophatidyl-choline and hydrogenated soy phosphatidylcholine, were more stable than those composed of lipids with lower phase transition temperatures. Incorporating distearoyl phosphatidylethanolamine-poly (ethylene glycol)(2000) into liposomes helped to reduce the size of the liposomes. In addition, the retention of a drug within liposomes was found to be slightly enhanced by including dimyristoylphosphatidylglycerol or dextran sulfate in the liposome formulation.