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

Topics 1. Models for Skin Absorption and Skin Toxicity Testing. 2. Models of the Small Intestine. 3. Drug Absorption from the Colon In Situ. 4. In Vivo and In Vitro Models for Assessing Drug Absorption Across the Bucal Mucosa. 5. In Situ and Ex Vivo Nasal Models for Preclinical Drug Development Studies. 6. The Isolated Perfused Lung for Drug Absorption Studies. 7. In Vitro Models for Investigations of Buccal Drug Permeation and Metabolism. 8. In Vitro Screening Models to Assess Intestinal Drug Absorption and Metabolism. 9. In Vitro Cellular Models for Nasal Drug Absorption Studies. 10. In Vitro Models of the Tracheo-Bronchial Epithelium. 11. In Vitro Models of the Alveolar Epithelial Barrier. 12. Cell Culture Models of the Corneal Epithelium and Reconstructed Cornea Equivalents for In Vitro Drug Absorption Studies. 13. The Conjunctival Barrier in Ocular Drug Delivery. 14. Inner Blood-Retinal Barrier : Transport Biology and Methodology. 15. Regulation of Paracellular Permeability in Low-Resistance Human Vaginal-Cervical Epithelia. 16. In Vitro Models and Multidrug Resistance Mechanisms of the Placental Barrier. 17. In Vitro Models to Study Blood-Brain Barrier Function. 18. High-Throughput Screening Using Caco-2 Cell and PAMPA Systems. 19. Instrumented In Vitro Approaches to Assess Epithelial Permeability of Drugs from Pharmaceutical Formulations. 20. Modeling Trandermal Absorption. 21. Physiologically Based in Silico Models for the Prediction of Oral Drug Absorption. 22. In Silico Modeling for Blood-Brain Barrier Permeability Predictions. 23. Impact of Drug Transport Proteins. 24. Cloning and Functional Heterologous Expression of Transporters. 25. The Pharmacology of Caveolae. 26. Immortalization Strategies for Epithelial Cells in Primary Culture. 27. Binding-Uptake Studies and Cellular Targeting. 28. Drug Permeability Studies in Regulatory Biowaiver Applications.

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. - Serves as an essential working handbook aimed at scientists and students in medicinal chemistry - Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies - Discusses improvements in pharmacokinetics from a practical chemist's standpoint

The development of new CNS drugs is notoriously difficult. Drugs must reach CNS target sites for action and these sites are protected by a number of barriers, the most important being the blood –brain barrier (BBB). Many factors are therefore critical to consider for CNS drug delivery, e.g. active/passive transport across the BBB, intra-brain distribution, and central/systemic pharmacokinetics, to name a few. Neurological disease and trauma conditions add further complexity because CNS barriers, drug distribution and pharmacokinetics are dynamic and often changed by disease/trauma. Knowledge of all these factors and their interplay in different conditions is of utmost importance for proper CNS drug development and disease treatment. In recent years much information has become available for a better understanding of the many factors important for CNS drug delivery and how they interact to affect drug action. This book describes small and large drug delivery to the brain with an emphasis on the physiology of the BBB and the principles and concepts for drug delivery across the BBB and distribution within the brain. It contains methods descriptions for studying drug delivery, routes and approaches of administering drugs into the brain, the influence of disease, and drug industry perspectives. Therewith, it contributes to an in-depth understanding of the interplay between brain (patho)-physiology and drug characteristics. Furthermore, the content is designed to be both cutting-edge and educational, so that the book can be used in high-level training of academic and industry scientists with full references to original publications. ​

This is a well thought-out, highly practical text covering contemporary ‘in vitro’ techniques for drug absorption studies. Starting at the molecular level of investigation, it continues with cell monolayer models (both primary and cell lines) and culminates with in situ techniques as a final testing format. In addition, chapters on high-throughput assays, in vitro-in vivo correlation, bioinformatics and regulatory issues are covered, giving a comprehensive overview of available models and techniques. Moreover, an appendix consisting of a number of practical protocols is available online, updated as needed, and should prove very helpful to apply the techniques directly to the benchside.

Basic Principles of Drug Discovery and Development presents the multifaceted process of identifying a new drug in the modern era, which requires a multidisciplinary team approach with input from medicinal chemists, biologists, pharmacologists, drug metabolism experts, toxicologists, clinicians, and a host of experts from numerous additional fields. Enabling technologies such as high throughput screening, structure-based drug design, molecular modeling, pharmaceutical profiling, and translational medicine are critical to the successful development of marketable therapeutics. Given the wide range of disciplines and techniques that are required for cutting edge drug discovery and development, a scientist must master their own fields as well as have a fundamental understanding of their collaborator's fields. This book bridges the knowledge gaps that invariably lead to communication issues in a new scientist's early career, providing a fundamental understanding of the various techniques and disciplines required for the multifaceted endeavor of drug research and development. It provides students, new industrial scientists, and academics with a basic understanding of the drug discovery and development process. The fully updated text provides an excellent overview of the process and includes chapters on important drug targets by class, in vitro screening methods, medicinal chemistry strategies in drug design, principles of in vivo pharmacokinetics and pharmacodynamics, animal models of disease states, clinical trial basics, and selected business aspects of the drug discovery process. - Provides a clear explanation of how the pharmaceutical industry works, as well as the complete drug discovery and development process, from obtaining a lead, to testing the bioactivity, to producing the drug, and protecting the intellectual property - Includes a new chapter on the discovery and development of biologics (antibodies proteins, antibody/receptor complexes, antibody drug conjugates), a growing and important area of the pharmaceutical industry landscape - Features a new section on formulations, including a discussion of IV formulations suitable for human clinical trials, as well as the application of nanotechnology and the use of transdermal patch technology for drug delivery - Updated chapter with new case studies includes additional modern examples of drug discovery through high through-put screening, fragment-based drug design, and computational chemistry

Explore this comprehensive discussion of the application of physiologically- and physicochemical-based models to guide drug delivery edited by leading experts in the field Drug Delivery Approaches: Perspectives from Pharmacokinetics and Pharmacodynamics delivers a thorough discussion of drug delivery options to achieve target profiles and approaches as defined by physical and pharmacokinetic models. The book offers an overview of drug absorption and physiological models, chapters on oral delivery routes with a focus on both PBPK and multiple dosage form options. It also provides an explanation of the pharmacokinetics of the formulation of drugs delivered by systemic transdermal routes. The distinguished editors have included practical and accessible resources that address the biological and delivery approaches to pulmonary and mucosal delivery of drugs. Emergency care settings are also described, with explorations of the relationship between parenteral infusion profiles and PK/PD. The future of drug delivery is addressed via discussions of virtual experiments to elucidate mechanisms and approaches to drug delivery and personalized medicine. Readers will also benefit from the inclusion of: A thorough introduction to the utility of mathematical models in drug development and delivery An exploration of the techniques and applications of physiologically based models to drug delivery Discussions of oral delivery and pharmacokinetic models and oral site-directed delivery A review of integrated transdermal delivery and pharmacokinetics in development An examination of virtual experiment methods for integrating pharmacokinetic, pharmacodynamic, and drug delivery mechanisms Alternative endpoints to pharmacokinetics for topical delivery Perfect for researchers, industrial scientists, graduate students, and postdoctoral students in the area of pharmaceutical science and engineering, Drug Delivery Approaches: Perspectives from Pharmacokinetics and Pharmacodynamics will also earn a place in the libraries of formulators, pharmacokineticists, and clinical pharmacologists.