Simultaneous separation and analysis of multiple doxorubicin hydrochloride liposomes forms in serum by circular nonuniform electric field gel electrophoresis

脂质体 化学 色谱法 药代动力学 电泳 阿霉素 剂型 药品 药理学 生物化学 化疗 医学 外科
作者
Peng Xie,Xiaoguang Yang,Zakia Fatima,Ruilin Yang,Huaze Sun,Yuhang Xing,Xiangdong Xu,Jingkai Gu,Lu Liu,Donghao Li
出处
期刊:Analytica Chimica Acta [Elsevier BV]
卷期号:1287: 342110-342110
标识
DOI:10.1016/j.aca.2023.342110
摘要

Liposomal formulations have traditionally been considered the most therapeutically effective drug delivery systems (DDS). However, their pharmacokinetics study and efficacy assessment are still challenging given size heterogeneity and unknown forms in vivo. The pharmacodynamic evaluation that solely analyzes total drug concentration is unfit for the liposomal formulation study. Hence, it is crucial to develop effective strategies for the separation and analysis of different forms of liposomal formulations in order to contribute to the study of pharmacokinetic profiles associated with both liposome-incorporated and non-liposomal drugs. (84) A laboratory-built circular nonuniform electric field gel electrophoresis (CNEFGE) system was developed in this study for simultaneous separation and analysis of various forms of doxorubicin hydrochloride (DOX•HCl) liposomes. Liposomes were effectively fractionized based on their size and higher concentration in situ in the concentration zone, obtaining liposome recovery >95 % and a 3.04 concentration factor. It was found that the technique could be used to evaluate not only the size distribution of liposomes but also the drug loading capacity related to size. The charge-to-size-based separation mechanism has also allowed the simultaneous separation of liposome-entrapped drugs, protein-bound drugs, and free drugs in various forms, and the technique has been successfully employed in serum. Moreover, the quantification analysis of liposomes incubated with serum for 72 h showed that the proportion of the ratio of DOX•HCl in liposome-entrapped drugs, protein-bound drugs, and free drugs is approximately 97:2:1. (143) Using the separation principle of gel electrophoresis and the electrification characteristics of drug carriers, this study developed and implemented an efficient approach for the simultaneous separation and concentration of multiple forms of drug liposomes in vivo. This approach offers a wide range of applications in the pharmacokinetics, efficacy, and safety evaluation of drug carriers and liposomes. (56).
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