Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy.

Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy.
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DOI:
10.1016/j.jconrel.2012.04.045
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发表时间:
2012-12-10
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Takayama S
Takayama S
中科院分区:
其他
文献类型:
--
作者:
Mehta G;Hsiao AY;Ingram M;Luker GD;Takayama S

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多细胞球体是体外微尺度的三维组织类似物。本文探讨了球体作为测试药物递送系统的体外平台的适用性。球体模拟体内存在的关键生理参数,包括复杂的多细胞结构、物质运输障碍以及细胞外基质沉积。相对于二维培养,球体还为药物测试提供了更好的靶细胞,是研究药物渗透的合适体外模型。文章强调了与制造大小均匀的球体、细胞数量少的球体以及共培养球体相关的关键挑战。此外,还讨论了表征球体中药物递送和功效所需的检测技术以及与此类研究相关的挑战。还强调了球体在药物递送和测试中的应用实例。鉴于这些挑战和可能的解决方案,多细胞球体正成为一种对病理组织和器官进行药物筛选和递送越来越有用的体外工具。
Multicellular spheroids are three dimensional in vitro microscale tissue analogs. The current article examines the suitability of spheroids as an in vitro platform for testing drug delivery systems. Spheroids model critical physiologic parameters present in vivo, including complex multicellular architecture, barriers to mass transport, and extracellular matrix deposition. Relative to two-dimensional cultures, spheroids also provide better target cells for drug testing and are appropriate in vitro model for studies of drug penetration. Key challenges associated with creation of uniformly sized spheroids, spheroids with small number of cells and co-culture spheroids are emphasized in the article. Moreover, the assay techniques required for the characterization of drug delivery and efficacy in spheroids and the challenges associated with such studies are discussed. Examples for the use of spheroids in drug delivery and testing are also emphasized. With these challenges and the possible solutions, multicellular spheroids are becoming an increasingly useful in vitro tool for drug screening and delivery to pathological tissues and organs.
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