Pharmaceutical Applications of Cell and Tissue Culture to Drug Transport

In recent years there have been rapid advances in the growth and differentiation of mammalian cells in culture. This has led to increasing use of such in vitro systems in a wide variety of studies on fundamental aspects of cell structure and function, including normal growth and metabolism, mechanisms of differentiation and oncogenesis, mechanisms of protein and membrane synthesis and cell polarity. Recent advances in our ability to grow cells, including human cells, on permeable supports, to generate confluent cellular barriers with the morphological polarity corresponding to their in vivo counterparts has greatly facilitated such studies. In particular these new techniques have led to an increasing interest in the use of cell and tissue culture systems as a means for examining the transport of drugs across epithelial and endothelial barriers. An obvious question is whether these new in vitro methodologies will provide convenient systems that can substitute for and replace animal models. Various research groups both in academia and in the pharmaceutical industry have been investigating these types of methodologies in order to develop convenient well characterized systems that can be used to examine basic aspects of transcellular transport and to evaluate the permeability of drug molecules and delivery systems. Of particular note is use of confluent cell layers to study the transport of large molecules such as peptides and proteins produced through recombinant DNA technology. Front Matter....Pages i-xi Pharmaceutical Applications of Cell Culture: An Overview....Pages 1-14 Growth and Characterization of Cell and Tissue Cultures for the Study of Drug Transport....Pages 15-25 Differentiation of Human Colon Cancer Cells....Pages 27-37 Criteria for Evaluating and Choosing a Relevant Cell Line....Pages 39-49 Use of Fabricated Living Tissue and Organ Equivalents as Defined Higher Order Systems for the Study of Pharmacologic Responses to Test Substances....Pages 51-65 Intracellular Pathways; Exocytic and Endocytic Routes Relying upon Selective Vesicular Transport....Pages 67-76 Carrier-Mediated Transport of Bile Acids and Amino Acids in Caco-2 Cells....Pages 77-91 Passive Absorption of Drugs in Caco-2 Cells....Pages 93-105 Receptor-Mediated Transport of Cobalamin in Caco-2 Cells: Intracellular Localisation of Transcobalamin II....Pages 107-120 An in vitro Absorption Model System Based on Cell Monolayers (Intestine 407, MDBK)....Pages 121-139 Transferrin Endocytosis and Fluid Phase Uptake in the Differentiable Intestinal Cell Line HT-29....Pages 141-154 Culture of Human Goblet Cells....Pages 155-161 Endothelial Barriers....Pages 163-174 Transport of Drugs Across the Blood-Brain Barrier: In Vitro and in Vivo Strategies....Pages 175-189 Metabolism of Catecholamine Prodrugs by Cultured Bovine Brain Microvessel Endothelial Cells....Pages 191-201 Membrane Recycling, Adsorptive and Receptor-Mediated Endocytosis by Primary Bovine Cerebral Microvessel Endothelial Cell Monolayers in Vitro ....Pages 203-216 Lipoproteins and Reconstituted Blood-Brain Barrier....Pages 217-229 Regulation of the Myocardial Blood Supply by Adenosine and Adenine Nucleotides: Consequences of Newly Detected Barrier Functions of the Coronary Endothelium....Pages 231-245 Cultured Human Umbilical Vascular Endothelial Cells and Their Underlying Matrix as Models to Study Cell Adhesion....Pages 247-248 Human Nasal Epithelial Cultures....Pages 249-258 Experimental Models for Buccal and Sublingual Drug Absorption Including Epithelial Cell Multilayers and Monolayers....Pages 259-270 Effect of Culture Environment on Terminal Differentiation of Human Epidermal Keratinocytes....Pages 271-281 Human Keratinocyte Cell Lines....Pages 283-296 Regulation of Haemopoietic Cell Development....Pages 297-306 Multilineage Hematopoietic Expression in a Three-Dimensional Long Term Bone Marrow Culture System....Pages 307-320 Isolation, Culturing and in Vitro Activation of Liver Macrophages....Pages 321-330 In Vitro Evaluation of Macrophage Mediated Host Defenses against Neoplastic Disease....Pages 331-341 Microcarrier-Facilitated Cultures for Fibroblastic and Epithelial Cells....Pages 343-346 Strategies for Immortalising Human Primary Cells and the Steps That Lead to Immortality....Pages 347-354 Carcinogen Metabolism in Immortalised Human Cells Grown as Hybrid Cells in Culture....Pages 355-365 Application of Cell and Tissue Culture in the Pharmaceutical Industry?....Pages 367-374 Key Issues in the Use of Cell and Tissue Culture Systems....Pages 375-378 Back Matter....Pages 379-387