title: A critical assessment of in vitro tissue models for ADME and drug delivery.
abstract: Cultured cells are widely used in the evaluation of new drugs and drug delivery systems. Cells can be grown at different levels of complexity ranging from simple reductionist models to complex organotypic models. The models are based on primary, secondary or stem cell derived cell cultures. Generation of tissue mimics with cultured cells is a difficult task, because the tissues have well-defined morphology, complex protein expression patterns and multiple inter-linked functions. Development of organotypic cell culture models requires proper biomaterial matrix and cell culture protocols that are able to guide the cells to the correct phenotype. This review illustrates the critical features of the cell culture models and, then, selected models are discussed in more detail (epidermal, corneal epithelial, retinal pigment epithelium, and hepatocyte models). The cell models are critically evaluated paying attention to the level of characterization and reliability of in vivo translation. Properties of the cell models must be characterized in detail using multiple biological assays and broad sets of model drugs. Robust in vivo predictions can be achieved with well-characterized cell models that are used in combination with computational methods that will bridge the gap between in vitro cell experiments and physiological situation in vivo in the body.
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Kati-Sisko
authors.initials: KS
authors.lastname: Vellonen
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Melina
authors.initials: M
authors.lastname: Malinen
authors.affiliation: Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Eliisa
authors.initials: E
authors.lastname: Mannermaa
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Astrid
authors.initials: A
authors.lastname: Subrizi
authors.affiliation: Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Toropainen
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Lou
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Kidron
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Yliperttula
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland; School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
mesh_terms: D018929:Cell Culture Techniques; D016503:Drug Delivery Systems; D010599:Pharmacokinetics
keywords: Cell model; Corneal epithelium; Epidermis; Hepatocyte; In vitro in vivo correlation; RPE