A rapid and efficient technique for liposomal and nonliposomal drug pharmacokinetics studies using magnetic nanoprobes and its application to leakage kinetics of liposomes.
A rapid and efficient technique for liposomal and nonliposomal drug pharmacokinetics studies using magnetic nanoprobes and its application to leakage kinetics of liposomes.
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DOI：
10.1016/j.chroma.2018.10.038
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发表时间：
2018-12
期刊：
影响因子：
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通讯作者：
Yunna Chen;Lei Wang;Dongdong Guo;Chenming Sheng;Haozhi Dai;Xiaoyan Shi;Wenjing Zhang;Qianqian Huang;Can Peng;Weidong Chen
中科院分区：
文献类型：
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作者：
Yunna Chen;Lei Wang;Dongdong Guo;Chenming Sheng;Haozhi Dai;Xiaoyan Shi;Wenjing Zhang;Qianqian Huang;Can Peng;Weidong Chen
目前，脂质体的体内药代动力学研究主要是通过测定血浆中的药物总量来进行的。这种使用总药物量而不是游离药物量的方法实际上增加了表观暴露和表观生物分布。为了解决这个问题，我们开发了一种快速有效的方法，通过使用成熟的链霉亲和素功能的Fe3O4@PDA作为分离纳米探针，在磁场的存在下，有效地从血浆中分离超过75%的生物素标记的DTX-脂质体。分离过程仅需20 min，采用LC-MS/MS法测定血浆中脂质体中DTX的浓度，血浆中DTX浓度在5-5000 ng/mL范围内线性关系良好，相关系数为0.9989。本研究结果清楚地表明，非脂质体药物和总药物在体内的药代动力学参数不同。因此，传统的研究脂质体体内药代动力学的方法是不合理的，本文提出的新方法为研究脂质体的药代动力学提供了一种策略。
Currently, the pharmacokinetics of liposomes was researched in vivo by measuring the total amount of drug in plasma. This method of using the total drug amount instead of the free drug amount virtually increase the apparent exposure and apparent biological distribution. To solve this problem, we developed a rapid and efficient method by using well-established streptavidin-functional Fe3O4@PDA as the separation nanoprobes to efficiently isolate biotin-labeled DTX-liposomes over 75% from plasma in the presence of magnetic field. The isolation procedure takes only 20 min and the concentration of DTX in liposomes from plasma was determined by LC–MS/MS. The method for the determination of DTX in plasma was linear in the range of 5–5000 ng/mL, and the correlation coefficient was 0.9989. Results obtained in this study clearly demonstrated that the pharmacokinetic parameters of non-liposomal drug and total drug are different in vivo. Therefore, traditional method for studying the pharmacokinetics of liposomes in vivo is unreasonable, and the new method mentioned here provided a strategy for studying the pharmacokinetics of liposomes.