Concepts and Models for Drug Permeability Studies

Cell and Tissue based In Vitro Culture Models

2nd Edition - February 20, 2024
Authors: Bruno Sarmento, Catarina Leite Pereira, José Das Neves
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 1 5 5 1 0 - 9
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 5 5 1 1 - 6

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 fo… Read more

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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.

Cover image
Title page
Table of Contents
Copyright
Contributors
About the editors
Chapter 1. Introduction
Chapter 2. Importance and applications of cell- and tissue-based in vitro models for drug permeability screening in early stages of drug development
2.1. Introduction
2.2. General considerations
2.3. Drug transport
2.4. Permeability-absorption models
2.5. Emerging trends and frontiers
2.6. Methods for permeability calculation
2.7. Standardization of protocols for in vitro methods
2.8. The “three Rs” principle
2.9. Biosecurity systems
Section I. Cell-based in vitro culture models for drug permeability studies: Immortalized and primary isolated cells
Chapter 3.1. Cell-based in vitro models for buccal permeability studies
3.1.1. Introduction
3.1.2. Physiology of the buccal mucosa
3.1.3. In vitro buccal models
3.1.4. Conclusion
Chapter 3.2. Cell-based in vitro models for gastric permeability studies
3.2.1. The stomach as a natural barrier to absorption
3.2.2. Gastric drug delivery
3.2.3. Cellularized models of gastric permeability
Chapter 3.3. Cell-based in vitro models for intestinal permeability studies
3.3.1. Introduction
3.3.2. Physiology of the gastrointestinal tract
3.3.3. Intestinal barriers
3.3.4. Transport mechanisms
3.3.5. Cell-based in vitro models
3.3.6. Conclusions and future perspectives
Chapter 3.4. Cell-based in vitro models for nasal permeability studies
3.4.1. Introduction
3.4.2. The anatomy of the nasal cavity
3.4.3. The histology of the nasal cavity and its implication for drug delivery
3.4.4. In vitro models of the nasal epithelial barrier
3.4.5. Procedures for permeability studies in nasal cellular models
3.4.6. Conclusion
Chapter 3.5. Cell-based in vitro models for pulmonary permeability studies
3.5.1. Introduction
3.5.2. Primary cells
3.5.3. Cell lines
3.5.4. Complex in vitro models
3.5.5. Conclusion
Chapter 3.6. Cell-based in vitro models for vaginal permeability studies
3.6.1. Introduction
3.6.2. Anatomy of the female genital tract and mucosa
3.6.3. Human primary cells
3.6.4. Immortalized human cells forming monolayers (bi-/trilayers)
3.6.5. Commercially available 3D culture of nontransformed human vaginal-ectocervical epithelial cells
3.6.6. The impact of mucus on cell-based models
3.6.7. Concluding remarks
Chapter 3.7. Cell-based in vitro models for transcorneal permeability studies
3.7.1. Introduction
3.7.2. Corneal barrier
3.7.3. Cell-based permeability models
3.7.4. Commercially available in vitro human-derived corneal epithelial models
3.7.5. Microfluidic-based corneal models for drug development
3.7.6. Effect of ophthalmic excipients on corneal permeability
3.7.7. Effect of ophthalmic formulations on transcorneal permeability
3.7.8. Effect of ophthalmic nanoformulations on transcorneal permeability
3.7.9. Conclusions
Chapter 3.8. Cell-based in vitro models for dermal permeability studies
3.8.1. Introduction
3.8.2. Human skin and dermal permeability mechanism
3.8.3. Commercial in vitro models
3.8.4. Conclusions and future perspectives
Section II. Tissue-based in vitro and ex vivo models for drug permeability studies
Chapter 3.9. Tissue-based in vitro and ex vivo models for blood–brain barrier permeability studies
3.9.1. Blood–brain barrier as a protective unit of the central nervous system
3.9.2. Static models of the blood–brain barrier
3.9.3. Dynamic models of the blood–brain barrier
3.9.4. Induced pluripotent stem cell–based models
3.9.5. Conclusions
Chapter 3.10. Cell-based in vitro models for placental barrier permeability studies
3.10.1. Human placental anatomy and physiology
3.10.2. Human placental barrier
3.10.3. Transplacental transport mechanisms
3.10.4. Placental in vitro models
3.10.5. Conclusions
Chapter 4.1. Tissue-based in-vitro models for buccal permeability studies
4.1.1. Introduction
4.1.2. Oral mucosa
4.1.3. In vitro permeation models
4.1.4. Experimental conditions
4.1.5. Permeation data
4.1.6. Conclusions
Chapter 4.2. Tissue-based in vitro and ex vivo models for intestinal permeability studies
4.2.1. Introduction
4.2.2. Current tissue-based methodologies for intestinal permeability studies
4.2.3. Animal versus human intestinal tissue
4.2.4. In vivo versus in vitro correlations
4.2.5. Intestinal permeability studies using diseased tissues
4.2.6. New trends in permeability studies using tissue-based models
4.2.7. Conclusion
Chapter 4.3. Tissue-based in vitro and ex vivo models for nasal permeability studies
4.3.1. Brief description of anatomy and physiology of the nose
4.3.2. Nasal administration of drugs
4.3.3. Limitations of the in vivo models
4.3.4. In vitro models of nasal permeability
4.3.5. Ex vivo models of nasal permeability
4.3.6. Conclusion
Chapter 4.4. Tissue-based in vitro and ex vivo models for pulmonary permeability studies
4.4.1. Introduction
4.4.2. Lung physiology and tissue biology
4.4.3. Tissue-based models
4.4.4. Conclusions and future perspectives
Chapter 4.5. Tissue-based models for vaginal permeability studies
4.5.1. Introduction
4.5.2. Vaginal permeability and absorption
4.5.3. In vitro 3D organotypic models
4.5.4. Ex vivo mucosal models
4.5.5. Conclusions
Chapter 4.6. Tissue-based models for ocular permeability studies
4.6.1. Introduction
4.6.2. Ocular barriers after topical eye drop administration
4.6.3. Models for preclinical drug development
4.6.4. Diffusion cell assemblies
4.6.5. Conclusion
Chapter 4.7. Tissue-based in vitro and ex vivo models for dermal permeability studies
4.7.1. Introduction
4.7.2. Structure of the skin
4.7.3. Mechanisms of skin absorption
4.7.4. Mathematical principles in skin absorption
4.7.5. Conducting in vitro dermal absorption tests
4.7.6. Conclusions
Chapter 4.8. Tissue-based in vitro and ex vivo models for blood–brain barrier permeability studies
4.8.1. Introduction
4.8.2. Structure and function of BBB
4.8.3. Cerebral microvessels and their characteristics
4.8.4. Methods for cell isolation and immortalization
4.8.5. Cell-based in vitro BBB models and their properties necessary for drug permeability estimation
4.8.6. Immortalized endothelial cell lines
4.8.7. Static and dynamic models of BBB compared
4.8.8. Measurements of drug permeability
4.8.9. Conclusions and future developments
Chapter 4.9. Tissue-based ex vivo models for placental barrier permeability studies
4.9.1. Introduction
4.9.2. Ex vivo models for placental transport studies
4.9.3. Mathematical modeling of placental transport
4.9.4. Conclusion
Section III. Miniaturized models for drug permeability studies
Chapter 5.1. Organ-on-chip models for intestinal permeability studies
5.1.1. Anatomy and physiology of the small intestine
5.1.2. The need for intestinal permeability studies
5.1.3. Microfluidics and organ-on-chip systems
5.1.4. Intestine-on-chip models
5.1.5. Future perspectives
5.1.6. Conclusion
Chapter 5.2. Organ-on-chip models for pulmonary permeability studies
5.2.1. Introduction
5.2.2. The lung as a target of drug delivery
5.2.3. Drug transport in the lung—mechanisms of absorption
5.2.4. Cell-line (immortalized) “lung-on-chip” models
5.2.5. Primary culture “lung-on-chip” models
5.2.6. Mechanical stretch
5.2.7. Further developments
5.2.8. Challenges and future directions for LOC
5.2.9. Concluding remarks
Chapter 5.3. Organ-on-chip models for blood–brain barrier permeability studies
5.3.1. Introduction
5.3.2. State-of-the-art microfluidic BBB-on-chips
5.3.3. Applications of μBBB
5.3.4. Conclusion and future perspectives
Chapter 5.4. Organ-on-chip models for other mucosal permeability studies
5.4.1. Introduction
5.4.2. On-chip models of different mucosal tissues
5.4.3. Conclusions
Section IV. Complex models for drug permeability studies
Chapter 6.1. Multicompartmental dynamic models for permeability studies
6.1.1. Introduction
6.1.2. Microphysiological systems
6.1.3. Discussion and conclusions
Chapter 6.2. Organoid-based models for permeability studies
6.2.1. Introduction
6.2.2. Organoid models for intestinal permeability studies
6.2.3. Using organoids to model the blood–brain barrier
6.2.4. Challenges and future perspectives
Chapter 7. Correlation between cell- and tissue-based in vitro models for drug permeability screening with in vivo situation: modeling and functional extrapolation
7.1. Introduction
7.2. Empirical correlations
7.3. Physiologically based pharmacokinetic models
7.4. Conclusions
Index

Bruno Sarmento

BBruno Sarmento is Principal Investigator and Group Leader at Institute for Research and Innovation in Health (i3S), University of Porto (UP), and Invited Associate Professor at Instituto Universitário de Ciências da Saúde (IUCS), Portugal. His research is focused on the development of mucosal tissue engineering models to validate functionalized nanomedicines and to perform in vitro/in vivo correlation. He has also established functionalized nanomedicines for mucosal drug delivery of drug with poor mucosal bioavailability. He published more than 400 papers in international journals, most in top journals (20000 Scopus citations; H-index 73). He edited 5 books, participated in more than 50 invited/selected talks in national and international meetings and was awarded several distinctions. He has supervised/co-supervised 15 Post-Docs, 50 PhD students and 40 MSc students. He is editor of European Journal of Pharmaceutical Sciences, and member of the Editorial Advisory Board of several international journals, including the Journal of Controlled Release, Expert Opinion on Drug Delivery and Pharmaceutics. Bruno Sarmento was the first Chair of the Nanomedicine and Nanoscale Delivery Focus Group of the Controlled Release Society (CRS) and is now Director-at-Large of CRS and member of CRS College of Fellows.

Affiliations and expertise

Affiliated Investigator, INEB–Instituto de Engenharia Biomédica, University of Porto, Portugal and Assistant Professor, Pharmaceutical Technology, Department of Pharmaceutical Sciences, ISCS-N, Gandra, Portugal

Catarina Leite Pereira

Dr. Leite Pereira is a Junior Researcher at Institute for Research and Innovation in Health (i3S), University of Porto (UP). Her research focus on the development of advanced 3D in vitro models as preclinical tools for novel drugs/nanomedicines screening, using multi-compartmentalized in vitro systems. Throughout her path Catarina has been able to translate her scientific achievements into the publication of 27 papers in leading peer-reviewed journals (h-index: 15, >500 citations). The quality of the scientific production can be ascertained by the several selected oral presentations in prestigious international conferences and invitations to act as expert reviewer in international funding agencies.

Affiliations and expertise

Junior Researcher Research and Innovation in Health (i3S), University of Porto Portugal, Portugal

José Das Neves

Dr. das Neves is Assistant Researcher at Institute for Research and Innovation in Health (i3S), University of Porto (UP), and Invited Assistant Professor at Instituto Universitário de Ciências da Saúde (IUCS), Portugal. His research focuses on mucosal drug delivery, particularly via the vaginal and rectal routes. For instance, he developed and expanded on the use and understanding of cell- and tissue-based models for evaluating nanotechnology-based drug delivery systems for local therapy and prophylaxis. He is the author of 77 (h-Index: 53) peer-reviewed articles in the broad field of drug delivery, editor of four scientific books and guest editor of seven special issues in international journals. José also serves as editorial board member of international journal in the field of drug delivery and biological sciences (Pharmaceutics (MDPI), Nanomaterials (MDPI), PLOS ONE (PLoS), and Drug Delivery Letters (Bentham)), and as Director of Scientific Communications of the Controlled Release Society.

Affiliations and expertise

Assistant Researcher Institute for research and Innovation in Health (i3S), University of Porto, Portugal

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Concepts and Models for Drug Permeability Studies

Cell and Tissue based In Vitro Culture Models

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Bruno Sarmento

Catarina Leite Pereira

José Das Neves