Time Interval of Two Injections and First-Dose Dependent of Accelerated Blood Clearance Phenomenon Induced by PEGylated Liposomal Gambogenic Acid: The Contribution of PEG-Specific IgM.
Time Interval of Two Injections and First-Dose Dependent of Accelerated Blood Clearance Phenomenon Induced by PEGylated Liposomal Gambogenic Acid: The Contribution of PEG-Specific IgM.
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聚乙二醇化脂质体藤原酸诱导的加速血液清除现象的两次注射时间间隔和首次剂量依赖性：聚乙二醇特异性 IgM 的贡献。
DOI：
10.1016/j.xphs.2018.10.027
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发表时间：
2019
影响因子：
3.8
通讯作者：
Weidong Chen
中科院分区：
文献类型：
--
作者：
Fengling Wang;Xi Ye;Yifan Wu;Huihui Wang;Chengming Sheng;D. Peng;Weidong Chen
重复注射PEG化脂质体可导致长循环性质的消失，因为抗PEG IgM抗体的诱导被称为“加速血液清除（ABC）现象”。尽管当包封的药物是具有低细胞毒性的化学治疗剂时通常发生ABC现象，但几乎没有证据表明PEG化的草药衍生化合物在重复注射时加速血液清除。在此，我们研究了PEG化脂质体藤黄酸（PEG-GEA-L），一种模型PEG化脂质体草药提取物，在其重复注射给大鼠的血液浓度。我们发现注射之间的时间间隔对PEG-GEA-L诱导的ABC现象的大小有相当大的影响。当时间间隔从3天延长到7天时，ABC现象可以减弱。此外，其幅度增强，伴随着肝脏和脾脏中PEG-GEA-L蓄积的显著增加，呈首次剂量依赖性。一致地，抗PEG IgM的水平随着PEG-GEA-L的首次给药而显著增加，并且随着注射之间的延长时间间隔而降低，这意味着抗PEG IgM是ABC现象的主要贡献者。值得注意的是，肝脏抗PEG IgM的表达增加伴随着ABC现象诱导过程中外排转运蛋白表达的增加。
Repeated injection of PEGylated liposomes can cause the disappearance of long circulating property because of the induction of anti-PEG IgM antibody referred to as “accelerated blood clearance (ABC) phenomenon.” Although ABC phenomenon typically occurs when entrapped drugs are chemotherapeutic agent with low cytotoxic, there is little evidence of accelerated blood clearance of PEGylated herbal-derived compound on repeated injection. Herein, we investigated the blood concentration of PEGylated liposomal gambogenic acid (PEG-GEA-L), a model PEGylated liposomal herbal extract, on its repeated injection to rats. We found time interval between injections had considerable impact on the magnitude of ABC phenomenon induced by PEG-GEA-L. When time interval was prolonged from 3 days to 7 days, ABC phenomenon could be attenuated. Furthermore, its magnitude was enhanced accompanied by a marked rise in the accumulation of PEG-GEA-L in the liver and spleen in a first-dose–dependent manner. Consistently, the level of anti-PEG IgM significantly increased with the first dose of PEG-GEA-L and decreased with the extended time interval between injections, which implies anti-PEG IgM is a major contributor to the ABC phenomenon. Notably, the increased expression of liver anti-PEG IgM was accompanied by an increased expression of efflux transporters in the induction process of the ABC phenomenon.
DOI：
10.1016/0005-2736(91)90162-2
发表时间：
1991-11-18
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
LASIC, DD;MARTIN, FJ;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D
Pegylation作为改善基于纳米颗粒的药物和基因递送的策略。
影响因子：
16.1
作者：
Suk JS;Xu Q;Kim N;Hanes J;Ensign LM
通讯作者：
Ensign LM