title: High-content analysis for drug delivery and nanoparticle applications.
abstract: High-content analysis (HCA) provides quantitative multiparametric 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.
authors.affiliation: University College Dublin (UCD) School of Veterinary Medicine, Dublin 2, Ireland; UCD Conway Institute, Dublin 2, Ireland. Electronic address: David.Brayden@ucd.ie.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brayden
authors.affiliation: School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Cryan
authors.affiliation: UCD Centre for Bionano Interactions, School of Chemistry and Chemical Biology, Belfield, Dublin 4, Ireland.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
authors.affiliation: University College Dublin (UCD) School of Veterinary Medicine, Dublin 2, Ireland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Brien
authors.affiliation: UCD School of Biology and Environmental Sciences, Belfield, Dublin 4, Ireland; UCD Conway Institute, Dublin 2, Ireland.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Simpson
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D001681:Biological Assay; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry / Q000633:toxicity*; D057166:High-Throughput Screening Assays; D006801:Humans; D008163:Luminescent Measurements; D053758:Nanoparticles; D036103:Nanotechnology / Q000379:methods*; D011108:Polymers / Q000737:chemistry / Q000633:toxicity*; D018570:Risk Assessment; D013678:Technology, Pharmaceutical / Q000379:methods*; D018675:Toxicity Tests
chemical_list: D004337:Drug Carriers; D005079:Excipients; D011108:Polymers