Repeated injections of PEGylated liposomal topotecan induces accelerated blood clearance phenomenon in rats

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• 作者：Yanling Ma^a ; Qiang Yang^a ; Long Wang^a ; Xinyu Zhou^b ; Yongxue Zhao^a ; Yihui Deng^a ; ^{dds-666-happy@163.com}
• 关键词：Polyethylene glycol (PEG) ; Accelerate blood clearance (ABC) phenomenon ; PEGylated liposomes ; Topotecan
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2012
• 期刊代码：15_09280987
• 类别：pha
• 出版时间：11 April, 2012
• 卷：45
• 期：5
• 页码：539-545
• 文件大小：774 K

摘要

The 鈥渁ccelerated blood clearance (ABC) phenomenon鈥?of PEGylated liposomes following multiple injections has been reported recently. This immunogenicity poses a problem for research into liposomes and hinders their clinical application. However, since doxorubicin liposomes and mitoxantrone liposomes have been reported to fail to induce the ABC phenomenon, some people believe that cytotoxic drugs loaded liposomes will not produce this ABC phenomenon under multiple-dosing regimens. Nevertheless, in the present study, we report that a first injection of the PEGylated liposomal topotecan (a cell cycle-specific drug for the S phase) still produced a strong ABC phenomenon. Likewise, when the first dose of 鈥渆mpty鈥?PEGylated liposomes or topotecan liposomes was increased, the ABC phenomenon of the subsequent dose was accordingly attenuated. Unlike doxorubicin and mitoxantrone, the blood clearance rate of topotecan was dramatically rapid, and the hepatic and splenic accumulations of topotecan liposomes were anomalous because of the ABC phenomenon. These findings may present new challenges to the clinical application of formulations of cytotoxic drugs loaded liposomes that require repeated administrations.