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Concepts and Models for Drug Permeability Studies: Cell and Tissue Based in Vitro Culture Models, Second Edition, summarizes the most important developments in in vitro models for predicting the permeability of drugs. This book is structured around three different approaches, summarizing the most recent achievements regarding models comprising (i) immortalized cells with an intrinsic ability to grow as monolayers when seeded in permeable supports, (ii) primary cells isolated from living organisms and directly cultured as barrier monolayers, and (iii) tissue-based models constructed with cell lines and extracellular matrix that resembles the tridimensional structure of mucosae and other biological membranes, or animal/patient-derived tissues. Each model is covered in detail, including the protocol of generation and application for specific drugs/drug delivery systems. The equivalence between in vitro cell and tissue models and in vivo conditions is discussed, highlighting how each model may provisionally resemble different drug absorption route. Chapters included in the first edition were updated with relevant data published in recent years, while four new chapters were included to reflect new emerging directions and trends in drug permeability models. Concepts and Models for Drug Permeability Studies: Cell and Tissue Based in Vitro Culture Models, Second Edition, is a critical reference for drug discovery and drug formulation scientists interested in delivery systems intended for the administration of drugs through mucosal routes and other important tissue barriers (e.g. the BBB). Researchers studying mucosal biology can use this book to familiarize themselves and exploit the synergic effect of mucosal delivery systems and biomolecules. - Summarizes the current advances in the use of permeability models in drug transport - Covers the most important buccal, gastric, intestinal, pulmonary, nasal, vaginal, ocular, renal, skin, and blood–brain barrier in vitro models. Includes case studies to facilitate understanding of various concepts in computer-aided applications - Updates in the second edition include organ-on-chip devices, 3D advanced models (multiple layered tissues, organoids, etc.), and multicompartmentalized tissue models

Life on Earth began some 4 billion years ago when the first primitive prokaryotes managed to isolate themselves from the rather hostile environment. The immediate challenge that these first life forms faced was to ensure an optimal balance between two apparently mutually exclusive tasks – protection and separation from the extracellular milieu on the one hand and an efficient exchange of ions, energy sources and metabolites with the very same milieu on the other hand. The commencing evolutionary progress had to address even more challenging problems, such as how to delegate specific cell functions to discrete structures inside of the cell, called organelles (such as the nucleus), and, at the level of multi-cellular organisms, to ensure proper separation of different cell types (e.g. those found in different tissues and organs) while ensuring efficient communication between them. In fact, the human body is highly compartmentalized, from the cell level where local signals are generated and propagated in a highly ordered manner, to the whole body level. This book aims to introduce the interested reader to the universe of these complex segregated compartments in mammals. It discusses how the integrity of different types of barriers – endothelial, epithelial – is normally maintained and what could go wrong when these barriers'permeability becomes abnormally low or high in different disease states. We will focus on several such barriers, which are well studied and which are pivotal for a healthy well-being. In particular, we will focus on the skin, airways, the gut barrier, the endometrium, and cardiovascular and urinary systems. Special reference throughout the book will be made to several most novel groups of potential molecular candidates for the correction of barrier-related dysfunctions, in particular Transient Receptor Potential channels. Hence the title of the book has a triple meaning – a trip in its common sense, TRP channels (as in TRiP database) and Translating Research Into Practice (TRIP). Our team of authors is comprised of physiologists, pharmacologists, biophysicists and medics, including the national representative of Ukraine in the European Crohn's and Colitis organization (ECCO) and a member of the Scientific Committee of the European Association of Urologists. We include clinical cases and discuss molecular and cellular mechanisms underlying such real-life problems in-depth.

This book intends to be an updated compilation of the most important buccal, gastric, intestinal, pulmonary, nasal, vaginal, ocular, skin and blood-brain barrier in vitro models for predicting the permeability of drugs. Concepts and Models for Drug Permeability Studies focuses on different approaches and comprises of various models. Each model describes the protocol of seeding and conservation, the application for specific drugs, and takes into account the maintenance of physiologic characteristics and functionality of epithelium, from the simplest immortalized cell-based monoculture to the most complex engineered-tissue models. Chapters also discuss the equivalence between in vitro cell and tissue models and in vivo conditions, highlighting how each model may provisionally resemble a different drug absorption route. - Updated information regarding the most recent in vitro models to study the permeability of drugs - Short and concise chapters covering all the biological barriers with interest in drug permeability - A combination of bibliographic information related with individual models and footnote instructions of technical procedures for construction of cell and tissue-based models - Simple and clear scientific content, adaptable for young scientists and experimented researchers

Epithelial cells are present in many different tissues in the body, and possess a diverse number of functional properties. However, all epithelial cells share some common characteristics. The cells possess a morphological polarity (an-apical and basolateral surface), and are interconnected by tight junctions. The epithelial cells also possess the capacity to transport select solutes across the monolayer. Transport systems localized on either the apical or basolateral surface are respon­ sible for this vectorial transport. Such characteristics of epithelial cells can be examined in the tissue culture situation. This volume discusses the use of cell culture techniques to study these fundamental properties of epithelial cells. Ma­ jor questions concerning epithelia which may be examined in culture are ad­ dressed. The approaches which are taken to answer these questions are described in detail with regards to kidney cell cultures. Similar investigations may be done with epithelial cell cultures derived from other tissues, following the kidney cell culture paradigm.

Epithelial cells exhibit an apical–basolateral axis of polarity that is generated during embryogenesis, is maintained throughout adult life in the face of constant cell regeneration, and is perturbed in several epithelial-associated diseases. We examine the structural and functional organization of epithelial tissues, as well as the events critical for generating epithelial asymmetry including vectorial trafficking of proteins and lipids, association of signaling and polarity proteins with subdomains of the plasma membrane, and 3D orientation of epithelial cells in response to cell–cell and cell–matrix interactions. As a paradigm to understand how these three processes are coordinated in time and space, we explore apical lumen formation. We also examine the final steps in epithelial morphogenesis, including brush border morphogenesis and ciliogenesis. Finally, we provide examples of disease processes that result from defects in epithelial polarity including diabetes insipidus, microvillar inclusion disease, hereditary deafness, ciliopathies, and cancer.

Epithelia are one of the commonest tissue types in the animal kingdom. Chapters from leading scientists in the major international research laboratories use examples from different systems to illustrate the form and function of epithelia. An important theme is the way in which epithelial cells differentiate to specialized tissue - reversal of this process occurs when cells become tumorigenic.

Building from general principles, the authors clearly explain the fundamental role of epithelia in plasma electrolyte and water balance. Emphasis is placed on experimental approaches and methodology. A comprehensive glossary of terms is included.

CACO-2 cell cultures are widely used in vitro models in several scientific fields such as nutrition, physiopathology, pharmacology, and toxicology. When cultured onto filters, these cells form a highly polarized epithelium that allows discrimination between apical and basolateral compartments. This new book presents topical research in the study of CACO-2 cells and their uses. Topics discussed include the application of CACO-2 cell models as a supportive in vitro tool during drug discovery and formulation; co-culture systems with CACO-2 cells to evaluate the bioactivity of plant extracts and the use of CACO-2 cells in intestinal transport, cell-matrix interactions and wound healing in intestinal villus cells.

Biological cell membranes regulate the transfer of matter and information between the intracellular and extracellular compartments as basic survival and maintenance functions for an organism. This volume contains a series of reviews that are c- cerned with how epithelial plasma membranes regulate the transport of solutes between the intracellular and extracellular compartments of a cell. This book is also an attempt to analyze the molecular basis for the movement of various solutes across an epithelial cell membrane. This volume is devoted to a diversity of epithelial transport mechanisms in rep- sentative cell membranes of a variety of living things. The?rst section of the book (Chapters 1–6) focuses on mechanisms of solute transport in epithelia of inver- brates. The last section which comprises ten chapters (Chapters 7–16) deals with solute transporters in epithelial cell membranes of vertebrates. It is hoped that with this particular ordering the reader can glean a telescopic view of the evolutionary history of the various epithelial solute transporters.

The understanding of the role of dendritic cells (DCs) in immune responses has come a long way since Steinmann and colleagues described these cells in 1972. - tensive research during the intervening period has provided a good understanding of the complexity of the DC system and its pivotal role in immunity. It is also now clearer how different subsets of DCs interact and regulate each other and how DC populations affect the function of other cells of the immune system. The improved understanding of their role in immune response has led to the idea that modulation of DC functions by, for example, pharmacological agents could be used as a pot- tial therapeutic approach in some pathological conditions. The actual applicability and therapeutic potential of all these approaches is yet to be fully demonstrated but nonetheless, animal models of human diseases are proving to be very helpful in the evaluation of manipulated DCs as a new treatment in diseases like cancer, auto- munity or asthma. DCs are integral to the initiation and regulation of immune response (Banchereau et al. 2000). The outcome of antigen presentation by DCs is determined by their maturation status, which can be induced by their interaction with danger signals. To recognise a wide array of pathogen-associated molecular patterns (PAMP), DCs express a number of pattern recognition receptors (PRR) such as Toll-like rec- tors (TLRs) and C-type lectin receptors (CLR) that recognise structural components of pathogens and discriminate between self and non-self molecules.

Great advances have taken place in basic research and the clinical usefulness of dendritic cells (DCs). It has now been clearly established, for instance, that these cells play a crucial role in immune responses against infectious diseases and cancers. Antigen-presenting DCs are widely distributed in the body and regulate both immunity and immune tolerance. Experimental studies have provided important insights into DCs and how they can be used for treating animal models of various diseases that occur in humans. The role of these cells in pathogenesis and the treatment of human diseases is elaborately set forth in this valuable book. Researchers in the field are optimistic that DCs, already in use for treating patients with cancers, soon can be used therapeutically for patients with chronic infections, autoimmune diseases, and allergic manifestations. This volume provides a working definition of DCs and also explains the phenotypes and functions of DCs so that these can be readily understood not only by clinicians but by immunologists, researchers, and students as well.

'This is essential reading for everyone who would like to update their knowledge of the pulmonary epithelium. It offers a comparison between laboratory animal models and human lungs, highlighting the differences and the similarities between the two, which will be particularly useful to researchers.'–Doody's, April 2009 The past two decades have seen extraordinary advances in our understanding of the role of the pulmonary epithelium in airway health and disease. Our understanding of epithelial biology has expanded exponentially in the past decade. This book provides a unique comprehensive description of the structure of the epithelium, its damage by various agents and the mechanism of epithelial repair. In addition, it's detailed coverage includes not only the multiple ways in which the epithelium contributes to host defence, but also the nature and functional consequences of the interactions of inhaled pathogens, including viruses, bacteria, allergens and pollutants. the role of the epithelium in regulating airway inflammation and structure is also discussed, as is the role of the epithelium as a target for inhaled medications and as a route for novel drug delivery. Containing chapters on multiple aspects of epithelial function in health and disease, each one is written by a leader in the field. This is essential reading for pulmonary researchers and physicians requiring detailed advanced understanding of the epithelium as well as those working in allergy, biomedical and pharmaceutical research.