Quantitative evaluation of liposomal doxorubicin and its metabolites in spheroids
Quantitative evaluation of liposomal doxorubicin and its metabolites in spheroids
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DOI：
10.1007/s00216-019-02084-7
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发表时间：
2019-11-01
影响因子：
4.3
通讯作者：
Hummon, Amanda B.
中科院分区：
文献类型：
--
作者：
Lukowski, Jessica K.;Hummon, Amanda B.
准确测量和了解治疗吸收和代谢是药物开发过程的关键。这项工作检查了与游离药物相比，封装在脂质体结构中后可以渗透到球体中的阿霉素的量。通过连续胰蛋白酶消化的过程，成功分离了球体的三个不同细胞群，并使用小分子提取来分离化疗药物。阿霉素显示出对球体的时间依赖性渗透性，在处理 24 小时时，大部分药物积聚在核心中。化疗药物的包埋延迟了药物的渗透性，导致早期时间点定量的量减少。这些发现证实了脂质体疗法能够改变药物的药代动力学和药效学特征的说法，同时还证明了质谱法和三维细胞培养物在评估药物渗透和代谢方面的综合能力。图形摘要
Accurate measurement and understanding of therapeutic uptake and metabolism is key in the drug development process. This work examines the amount of doxorubicin that can penetrate into spheroids after being encapsulated in a liposomal configuration in comparison with free drug. Through a process known as serial trypsinization, three distinct cellular populations of a spheroid were successfully separated and a small molecule extraction was used to isolate the chemotherapeutic. Doxorubicin showed a time-dependent permeability into spheroids with the most drug accumulating in the core at 24 h of treatment. Entrapment of the chemotherapeutic delayed the permeability of the drug and resulted in reduced amounts quantified at the earlier time points. These findings validate the claim that liposomal therapeutics have the ability to alter the pharmacokinetics and pharmacodynamics profiles of a drug while also demonstrating the combined power of mass spectrometry and three-dimensional cell cultures to evaluate drug penetration and metabolism.Graphical abstract