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

JOURNAL OF CONTROLLED RELEASE

卷:164

Article

Mehta, Geeta^1,2  Ingram, Marylou³  Luker, Gary D.^4,5  Takayama, Shuichi^6,7 

[1] Univ Michigan, Dept Biomed Engn, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA

[3] Huntington Med Res Inst, Pasadena, CA 91101 USA

[4] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Dept Macromol Sci & Engn, Ann Arbor, MI 48109 USA

[7] UNIST, WCU Project, Div Nanobio & Chem Engn, Ulsan, South Korea

关键词: Spheroids;    Drug delivery;    Drug screening;    High throughput;    Tissue engineering;    Imaging;   

DOI  :  10.1016/j.jconrel.2012.04.045

来源: Elsevier

【 摘 要 】

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 models 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. By addressing these challenges with possible solutions, multicellular spheroids are becoming an increasingly useful in vitro tool for drug screening and delivery to pathological tissues and organs. (c) 2012 Elsevier B.V. All rights reserved.

【 授权许可】

Free