Zhang Ting, Zhou Songlei, Kang Le, Luo Xiang, Liu Yang, Song Yanzhi, Liu Xinrong, Deng Yihui
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Asian J Pharm Sci. 2017 Mar;12(2):134-142. doi: 10.1016/j.ajps.2016.06.005. Epub 2016 Aug 4.
PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. However, PEG-modified liposomes can induce accelerated blood clearance (ABC) upon repeated administration, and the extent of ABC phenomenon on the cytotoxic drugs-containing PEGylated liposomes is related to the dose of the cytotoxic drugs. In this study, EPI served as a model cytotoxic drug, a hydrophilic surfactant molecule, monosialylganglioside (GM1) was chosen and modified on the liposomes together with PEG. It was shown that upon mixed modification, when GM1 contents reached 10% or 15% mol, the ABC phenomenon of the PEGylated liposomal EPI significantly reduced. We also found that GM1 played an important role in abrogating the ABC phenomenon in both the induction phase and the effectuation phase. The results suggested that GM1 incorporation unfortunately did not avoid occurrence of ABC phenomenon completely, but GM1 modification on PEGylated liposomes may provide a significant improvement in clinical practice of PEGylated liposomes. Further study must be necessary.
聚乙二醇化脂质体是改善包封药物药代动力学特性、延长其循环半衰期并促进其在肿瘤部位被动蓄积的潜在候选物。然而，聚乙二醇修饰的脂质体在重复给药后可诱导加速血液清除（ABC）现象，且含细胞毒性药物的聚乙二醇化脂质体上ABC现象的程度与细胞毒性药物的剂量有关。在本研究中，表柔比星（EPI）作为模型细胞毒性药物，选择了一种亲水性表面活性剂分子单唾液酸神经节苷脂（GM1）并与聚乙二醇一起在脂质体上进行修饰。结果表明，混合修饰时，当GM1含量达到10%或15%摩尔时，聚乙二醇化脂质体EPI的ABC现象显著降低。我们还发现GM1在消除ABC现象的诱导期和效应期均发挥重要作用。结果提示，GM1的掺入遗憾地未能完全避免ABC现象的发生，但聚乙二醇化脂质体上的GM1修饰可能在聚乙二醇化脂质体的临床应用中带来显著改善。进一步的研究是必要的。
