High-content analysis for drug delivery and nanoparticle applications

被引:32
作者
Brayden, David J. [1 ,2 ]
Cryan, Sally-Ann [3 ,4 ]
Dawson, Kenneth A. [5 ]
O'Brien, Peter J. [1 ]
Simpson, Jeremy C. [2 ,6 ]
机构
[1] Univ Coll Dublin, Sch Vet Med, Dublin 2, Ireland
[2] UCD Conway Inst, Dublin 2, Ireland
[3] Royal Coll Surgeons Ireland, Sch Pharm, Dublin 2, Ireland
[4] Univ Dublin Trinity Coll, Trinity Ctr Bioengn, Dublin 2, Ireland
[5] UCD Ctr Bionano Interact, Sch Chem & Chem Biol, Dublin 4, Ireland
[6] UCD Sch Biol & Environm Sci, Dublin 4, Ireland
基金
爱尔兰科学基金会;
关键词
INTESTINAL PERMEATION ENHANCERS; GENE-EXPRESSION ANALYSIS; IN-VITRO; INTRACELLULAR TRAFFICKING; POLYMERIC NANOPARTICLES; ABSORPTION ENHANCERS; HUMAN HEPATOTOXICITY; LIPID NANOPARTICLES; CYTOTOXICITY ASSAY; MECHANISTIC ASSAYS;
D O I
10.1016/j.drudis.2015.04.001
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
High-content analysis (HCA) provides quantitative multiparamehic cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents.
引用
收藏
页码:942 / 957
页数:16
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