Controlled application and scheduled removal of nanoparticle based chemotherapeutics (CARL) will reduce dose limiting adverse events in anticancer chemotherapy
Controlled application and scheduled removal of nanoparticle based chemotherapeutics (CARL) will reduce dose limiting adverse events in anticancer chemotherapy
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DOI：
10.1016/j.mehy.2008.11.027
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发表时间：
2009-04-01
影响因子：
4.7
通讯作者：
Winkler, Karl
中科院分区：
文献类型：
--
作者：
Puetz, Gerhard;Schmah, Oliver;Winkler, Karl
剂量限制性毒性损害了癌症化疗的临床成功。基于纳米颗粒的药物输送系统（DDS），如长循环脂质体，显示出改善的毒性特征。然而，它们独特的药代动力学特性会导致新的剂量限制性不良事件，例如皮肤毒性升高。尽管DDS在肿瘤组织中积累，但只有总剂量的一小部分到达目标部位。只需要大量的给定剂量即可建立扩散梯度，以便在目标部位有效积累。由于内皮屏障的改变，DDS在肿瘤组织中的积累比在其他组织中的积累快得多，在其他组织中会发生剂量限制性副作用。根据这些药代动力学数据，我们假设，一旦肿瘤组织中的积累完成，快速消除仍在血浆中循环的 DDS 部分可能会减少其他剂量限制性毒性。循环 DDS 的快速消除可能通过体外单采治疗来进行。本文详细介绍了通过预定的体外消除长循环 DDS 进行动力学靶向的原理。还讨论了对患者的益处以及可能的批评和未来的发展。总之，DDS 和预定单采术的结合可能允许开发具有更高影响和/或更低毒性的新化疗方案。 (C) 2008 Elsevier Ltd. 保留所有权利。
Clinical success of cancer chemotherapy is impaired by dose limiting toxicities. Nanoscale particle based drug delivery systems (DDS) like long circulating liposomes show improved toxicity profiles. Nevertheless, their unique pharmacokinetic properties lead to new dose limiting adverse events such as elevated skin toxicity, Though DDS accumulate in tumor tissue, only a very small fraction of the total dose reaches the target site. The overwhelming amount of a given dose is needed only to build up a diffusion gradient for effective accumulation at the target site. Due to the altered endothelial barrier, accumulation of DDS in tumor tissue is much faster than accumulation in other tissues, where dose limiting side effects occur. On the basis of these pharmakinetic data we hypothesize, that once accumulation in the tumor tissue is completed, rapid elimination of the DDS fraction still circulating in the plasma may diminish otherwise dose limiting toxicities.Rapid elimination of circulating DDS might be performed by extracorporeal apheresis treatment. Within this paper the principle of kinetic targeting by scheduled extracorporeal elimination of long circulating DDS is presented in detail. Benefits for patients are as well discussed as possible criticisms and future developments.In conclusion, the combination of DDS and scheduled apheresis may allow the development of new chemotherapy regiments with higher impact and/or less toxicity. (C) 2008 Elsevier Ltd. All rights reserved.