Effect of phospholipid composition on pharmacokinetics and biodistribution of epirubicin liposomes
Effect of phospholipid composition on pharmacokinetics and biodistribution of epirubicin liposomes
复制标题
磷脂组成对表阿霉素脂质体药代动力学和生物分布的影响
DOI：
10.3109/08982104.2011.627513
复制
发表时间：
2012-03-01
影响因子：
4.4
通讯作者：
Fang, Xiaoling
中科院分区：
文献类型：
--
作者：
Sha, Xianyi;Guo, Jie;Fang, Xiaoling
研究了磷脂成分对表柔比星 (EPI) 脂质体的药代动力学 (PK) 和生物分布以及各种脂质体制剂的体外巨噬细胞摄取的影响。研究了三种脂质体配方：HSPC:Chol（L-EPI；5:4 摩尔比）、HSPC:Chol:DSPG（D-EPI；5:4:1 摩尔比）和 HSPC:Chol:DSPG:DSPE-mPEG2000（S-EPI；5:4:1:0.3 摩尔比）。采用改进的薄膜水合法，通过聚碳酸酯滤膜挤出，制备小单层脂质体，并通过跨膜硫酸铵梯度法将EPI远程负载到脂质体中。巨噬细胞用于体外评估细胞对 EPI 负载脂质体的摄取。观察到摄取量的降序如下：L-EPI>D-EPI>S-EPI。 D-EPI 显示出相对较低的摄取水平，可能是由于 DSPG 上的甘油头基提供的空间位阻，保护其免受细胞膜受体的直接识别。随着血清的存在，所有脂质体制剂的摄取值都会增加，以激活补体系统。在 PK 研究中，S-EPI 显示循环时间显着延长，清除率降低。在各种脂质体制剂中观察到浓度与时间曲线下面积的以下递增顺序：L-EPI<D-EPI<S-EPI。生物分布研究表明，与其他脂质体相比，S-EPI 减少了肝脏、脾脏、肺和心脏中的药物分布，并增加了肾脏中的药物分布。 S-EPI 在延长循环时间和降低心脏毒性方面的令人鼓舞的特性可能为临床应用提供了一个有前景的前景，所有结果都将支持对基于脂质体的药物载体的进一步研究。
The effects of phospholipid composition on the pharmacokinetics (PK) and biodistribution of epirubicin (EPI) liposomes, as well as the in vitro macrophage uptake of various liposome formulations, were investigated. Three liposome formulations were investigated: HSPC:Chol (L-EPI; 5:4 molar ratio), HSPC:Chol:DSPG (D-EPI; 5:4:1 molar ratio), and HSPC:Chol:DSPG:DSPE-mPEG2000 (S-EPI; 5:4:1:0.3 molar ratio). Small unilamellar liposomes were prepared by the modified thin-film hydration method with extrusion through polycarbonate filters, and EPI was remote loaded into liposomes by the transmembrane ammonium sulfate gradient method. Macrophages were used to evaluate in vitro the cellular uptake of EPI-loaded liposomes. The following decreasing order of uptake amount was observed: L-EPI>D-EPI>S-EPI. D-EPI showed a relatively low level of uptake, probably because of the steric hindrance provided by the glycerol head group on DSPG, protecting it from the direct recognization by cell-membrane receptors. With the presence of serum, uptake values for all liposome formulations were increased for the activation of the complement system. In the PK study, S-EPI showed significantly prolonged circulating time and reduced clearance. The following increasing order of area under the concentration versus time curve was observed among the various liposome formulations: L-EPI<D-EPI<S-EPI. The biodistribution study indicated that S-EPI decreased drug disposition in the liver, spleen, lung, and heart and increased that in the kidney with respect to the other liposomes. The encouraging property of S-EPI, in terms of prolonging circulating time and reducing heart toxicity, might describe a promising perspective toward clinical application, and all the results would support further research into liposome-based drug carriers.