Concepts and Models for Drug Permeability Studies - 1st Edition - ISBN: 9780081000946, 9780081001141

Concepts and Models for Drug Permeability Studies

1st Edition

Cell and Tissue based In Vitro Culture Models

Authors: Bruno Sarmento
eBook ISBN: 9780081001141
Hardcover ISBN: 9780081000946
Imprint: Woodhead Publishing
Published Date: 1st October 2015
Page Count: 408
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Description

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.

Key Features

  • 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

Readership

The major target market is that of drug discovery and drug formulation scientists interested in drug delivery systems administered through mucosal routes. The book might also be particularly interesting to post-graduate students of biotechnology, pharmaceutical sciences, biochemistry, medicine or any related biomedical subject.

Table of Contents

  • List of contributors
  • List of figures
  • List of tables
  • 1. Introduction
    • 1.1. Introduction
  • 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. Methods for permeability calculation
    • 2.6. Standardization of protocols for in vitro methods
    • 2.7. The “three Rs” principle
    • 2.8. Biosecurity systems
  • 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. Different in vitro models
    • 3.1.4. Conclusions
  • 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
    • 3.2.4. Conclusions
  • 3.3. Cell-based in vitro models for intestinal permeability studies
    • 3.3.1. Anatomy and physiology of human small intestine
    • 3.3.2. Mechanisms of transport
    • 3.3.3. Intestinal barriers
    • 3.3.4. Intestinal in vitro models
    • 3.3.5. Validation studies
    • 3.3.6. Conclusions
  • 3.4. Cell-based in vitro models for nasal permeability studies
    • 3.4.1. Introduction
    • 3.4.2. Nasal primary cell culture models
    • 3.4.3. Immortalized nasal cell lines
    • 3.4.4. Nasal permeability studies
    • 3.4.5. Conclusions
  • 3.5. Cell-based in vitro models for pulmonary permeability studies
    • 3.5.1. Introduction
    • 3.5.2. Mechanisms involved in pulmonary absorption of drugs
    • 3.5.3. Cell-based models of immortalized cells
    • 3.5.4. Primary cell cultures
    • 3.5.5. Conclusions
  • 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-/tri-layers)
    • 3.6.5. Commercially available three-dimensional culture of nontransformed human vaginal-ectocervical epithelial cells
    • 3.6.6. Concluding remarks
  • 3.7. Cell-based in vitro models for ocular permeability studies
    • 3.7.1. Introduction
    • 3.7.2. Ocular anatomy
    • 3.7.3. Ocular pharmacokinetics in the anterior segment
    • 3.7.4. Ocular pharmacokinetics in the posterior segment
    • 3.7.5. In vitro eye cellular models for drug permeability
    • 3.7.6. Conclusions
  • 3.8. Cell-based in vitro models for dermal permeability studies
    • 3.8.1. Introduction
    • 3.8.2. Human skin and dermal permeability
    • 3.8.3. Drug permeability in in vitro models
    • 3.8.4. Reconstructed dermal equivalents
    • 3.8.5. Reconstructed full-thickness models
    • 3.8.6. Conclusions and future perspectives
  • 3.9. Cell-based in vitro models for studying blood–brain barrier (BBB) permeability
    • 3.9.1. Blood–brain barrier: structure, importance, and difficulties to overcome
    • 3.9.2. BBB in vitro models
    • 3.9.3. Permeability of drugs: how to screen and study
    • 3.9.4. Comparison of BBB models
  • 4.1. Tissue-based in vitro and ex vivo models for buccal permeability studies
    • 4.1.1. Introduction
    • 4.1.2. Porcine buccal mucosa
    • 4.1.3. Diffusion cells
    • 4.1.4. Permeation assay using porcine buccal mucosa
    • 4.1.5. Tissue integrity and viability assessment
    • 4.1.6. Porcine esophageal mucosa
    • 4.1.7. Conclusions and future prospects
  • 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. New trends in permeability studies using tissue-based models
    • 4.2.6. Conclusions
  • 4.3. Tissue-based in vitro and ex vivo models for nasal permeability studies
    • 4.3.1. Brief description of the structure of the nose
    • 4.3.2. Nasal administration of drugs
    • 4.3.3. Limitations of in vivo models
    • 4.3.4. In vitro models of nasal permeability
    • 4.3.5. Ex vivo models of nasal permeability
    • 4.3.6. Conclusions
  • 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. Isolated perfused lung
    • 4.4.4. Conclusions
  • 4.5. Tissue-based in vitro and ex vivo 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
  • 4.6. Tissue-based in vitro and ex vivo models for ocular permeability studies
    • 4.6.1. Introduction
    • 4.6.2. Requirements for a valid corneal cell culture model for in vitro drug absorption studies
    • 4.6.3. Methods to obtain corneal cells
    • 4.6.4. Methods to verify cultivated cell layers in the construct
    • 4.6.5. 3D reconstructed cornea models
    • 4.6.6. Discussions
    • 4.6.7. Conclusions
  • 4.7. Tissue-based in vitro and ex vivo models for dermal permeability studies
    • 4.7.1. Introduction
    • 4.7.2. Structure and function of the skin
    • 4.7.3. Mechanisms of skin absorption
    • 4.7.4. Mathematical principles of skin absorption
    • 4.7.5. Conducting in vitro dermal absorption tests
  • 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
  • 5. Correlation between cell- and tissue-based in vitro models for drug permeability screening with in vivo situation: Modeling and functional extrapolation
    • 5.1. Introduction
    • 5.2. Empirical correlations
    • 5.3. Physiologically based pharmacokinetic models
    • 5.4. Conclusions
  • Index

Details

No. of pages:
408
Language:
English
Copyright:
© Woodhead Publishing 2016
Published:
Imprint:
Woodhead Publishing
eBook ISBN:
9780081001141
Hardcover ISBN:
9780081000946

About the Author

Bruno Sarmento

Bruno Sarmento is an Affiliated Investigator at the INEB–Instituto de Engenharia Biomédica, based at the University of Porto, Portugal and is Assistant Professor of Pharmaceutical Technology in the Department of Pharmaceutical Sciences, at ISCS-N, Gandra, Portugal. His current research is focused on the study of nanomedicines and their application in the pharmaceutical and biomedical fields, as well as the use of in vitro cell models as a tool to correlate the transport of biopharmaceuticals and nanoparticles across human mucosa. Bruno has been involved with more than two hundred publications, including three edited books in the field of Pharmaceutical Technology and Nanomedicine, more than one hundred papers in international peer-review journals and several conference proceedings. He also serves as an editorial board member for several international journals and an evaluator of research projects form international agencies. He is an active member of several international associations (AAPS, CRS, EUFEPS, EFSD, FIP) and works on biotechnology and health post-graduate programs at national and international level.

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