title: Life in 3D is never flat: 3D models to optimise drug delivery.
abstract: The development of safe, effective and patient-acceptable drug products is an expensive and lengthy process and the risk of failure at different stages of the development life-cycle is high. Improved biopharmaceutical tools which are robust, easy to use and accurately predict the in vivo response are urgently required to help address these issues. In this review the advantages and challenges of in vitro 3D versus 2D cell culture models will be discussed in terms of evaluating new drug products at the pre-clinical development stage. Examples of models with a 3D architecture including scaffolds, cell-derived matrices, multicellular spheroids and biochips will be described. The ability to simulate the microenvironment of tumours and vital organs including the liver, kidney, heart and intestine which have major impact on drug absorption, distribution, metabolism and toxicity will be evaluated. Examples of the application of 3D models including a role in formulation development, pharmacokinetic profiling and toxicity testing will be critically assessed. Although utilisation of 3D cell culture models in the field of drug delivery is still in its infancy, the area is attracting high levels of interest and is likely to become a significant in vitro tool to assist in drug product development thus reducing the requirement for unnecessary animal studies.
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Fitzgerald
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Malhotra
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College, Dublin (TCD), Ireland; Advanced Materials and BioEngineering Research Centre (AMBER), RCSI & TCD, Dublin, Ireland.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Curtin
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College, Dublin (TCD), Ireland; Advanced Materials and BioEngineering Research Centre (AMBER), RCSI & TCD, Dublin, Ireland.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O' Brien
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland. Electronic address: caitriona.odriscoll@ucc.ie.
authors.forename: Caitriona M
authors.initials: CM
authors.lastname: O' Driscoll
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D021621:Imaging, Three-Dimensional; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology; D018874:Spheroids, Cellular; D046509:Tissue Culture Techniques
keywords: 3D cell culture; Biomaterials; Drug delivery; In vitro biopharmaceutical tool; The 3 Rs