PEG化脂质体30周年回顾与反思  

Review and reflection on the 30th anniversary of PEGylated liposome

作　　者：高新 李聪 刘梦阳[1] 闫鑫杨 宋艳志[1] 邓意辉[1] GAO Xin;LI Cong;LIU Mengyang;YAN Xinyang;SONG Yanzhi;DENG Yihui(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2022年第1期114-126,共13页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81973271)。

摘　　要：目的 回顾PEG化脂质体(PEGylated liposomes)首次报道至今30年来的相关研究,反思其临床安全性和有效性。方法 查阅国内外相关文献137篇,归纳、总结和分析PEG化脂质体的利弊。结果 聚乙二醇(polyethylene glycol, PEG)的修饰成功地延长了脂质体的血液循环时间,并且广泛应用于临床。目前,多种PEG化脂质体如ThermoDox^(■)、Lipoplatin^(TM)和MM-302等处于临床试验阶段。然而,研究表明,PEG化制剂可以诱导抗-PEG抗体的产生,抗-PEG抗体与临床上补体激活相关假变态反应(complement activation related pseudo allergy, CARPA)的发生密切相关。更严重的是,抗-PEG抗体在健康汉族人血液样本中的阳性检测率高达72%,已成为PEG化制剂临床应用面临的主要问题。结论 PEG化脂质体并不完美,已在人群中普遍存在的抗-PEG抗体会降低临床PEG化制剂的用药安全性和有效性,应该引起重视。Objective To review the relevant research of PEGylated liposomes over the past 30 years since the first report in 1990,and to reflect on the clinical safety and effectiveness of PEGylated liposomes for tumor delivery of drugs.Methods By referencing 137 domestic and overseas literatures, the advantages and disadvantages of PEGylated liposomes were summarized, analyzed and concluded.Results Although PEGylation that successfully prolonged the blood circulation time of liposomes and improved the biodistribution of drugs was widely used in clinics and many preparations such as ThermoDox^(■),Lipoplatin^(TM)and MM-302 were in clinical trials, PEGylated preparations could induce the production of anti-PEG antibodies that would be major risks for humans.The occurrence of pseudo-allergic reaction related to complement activation in clinic was closely related to anti-PEG antibodies.Anti-PEG antibodies were ubiquitous in healthy people, and the positive detection rate of human anti-PEG antibodies was as high as 72%.Anti-PEG antibodies had become an insurmountable problem in the clinical application of PEGylated liposomes.Conclusion PEGylated liposomes are not perfect because of the presence of anti-PEG antibodies that are prevalent in healthy people and may reduce the clinical safety and effectiveness of PEGylated liposomes.The related phenomenon should be worried.

关 键 词：脂质体 聚乙二醇化 加速血液清除现象 抗-PEG抗体 

分 类 号：R94[医药卫生—药剂学]