Concepts and models for drug permeability studies : cell and tissue based in vitro culture models / edited by Bruno Sarmento ; contributors Joao Albuquerque [and forty nine others].

Format:

Book

Contributor:

Sarmento, Bruno, editor.

Albuquerque, Joao, contributor.

Series:

Woodhead Publishing series in biomedicine ; Number 79.

Woodhead Publishing series in biomedicine ; Number 79

Language:

English

Subjects (All):

Drugs--Testing.

Drugs.

Drugs--Physiological transport--Research--Methodology.

Epithelial cells.

Cell culture.

Drug development.

Physical Description:

1 online resource (0 p.)

Place of Publication:

Amsterdam, [Netherlands] : Woodhead Publishing, 2016.

Language Note:

English

Summary:

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

Contents:

Front Cover

Related titles

Concepts and Models for Drug Permeability Studies

Copyright

Contents

List of contributors

List of figures

List of tables

1 - Introduction

1.1 Introduction

References

2 - Importance and applications of cell- and tissue-based in vitro models for drug permeability screening in early stages o ...

2.1 Introduction

2.2 General considerations

2.3 Drug transport

2.3.1 Transport mechanisms

2.4 Permeability-absorption models

2.4.1 Physicochemical methods

2.4.1.1 Physicochemical factors

2.4.1.2 Immobilized artificial membrane chromatography

2.4.1.3 Parallel artificial membrane permeability assay

2.4.2 In vitro cell and tissue methods

2.4.2.1 Cell-based methods

2.4.2.2 Tissue-based methods

Diffusion chambers

Franz cells

Everted sacs

Isolated membrane vesicles

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

3.1.3.1 Hamster cheek pouch cells

3.1.3.2 TR146 cell line

3.1.3.2.1 Protocol

Cell culture conditions

Permeability studies

3.1.3.3 Human oral keratinocytes

3.1.3.3.1 Protocol

Oral keratinocyte culture conditions

Culturing on dead de-epidermized dermis (DDED)

3.1.3.4 MatTek EpiOral™

3.1.3.4.1 Protocol

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

3.2.2.1 Molecular absorption in the stomach.

3.2.2.2 Physicochemical factors mediating stomach absorptive permeability

3.2.3 Cellularized models of gastric permeability

3.2.3.1 Protocol for establishing cellularized artificial models of the gastric wall

3.2.4 Conclusions

Acknowledgments

3.3 - Cell-based in vitro models for intestinal permeability studies

3.3.1 Anatomy and physiology of human small intestine

3.3.1.1 Stromal-epithelial cross-talk

3.3.2 Mechanisms of transport

3.3.3 Intestinal barriers

3.3.4 Intestinal in vitro models

3.3.4.1 Caco-2 model

3.3.4.1.1 Accelerated Caco-2 models

3.3.4.1.2 Alternatives to the Caco-2 model

3.3.4.2 Caco-2/HT29-MTX model

3.3.4.3 Caco-2/Raji B model

3.3.4.4 Caco-2/HT29-MTX/Raji B

3.3.4.5 Novel 3D 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

3.4.2.1 Sampling approaches and procedures

3.4.2.2 HNE cell preparation and culture initiation

3.4.3 Immortalized nasal cell lines

3.4.3.1 RMPI 2650 cell line

3.4.3.2 BT cell line

3.4.3.3 Human lung carcinoma cell line

3.4.3.4 Human normal bronchial epithelium of male heart-lung transplant patient 16HBE14o- cell line

3.4.4 Nasal permeability studies

3.4.4.1 Culture conditions

3.4.4.2 Cell-based permeation 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

3.5.3.1 Bronchial cell lines

3.5.3.2 Alveolar cell lines

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

3.6.3.1 Isolation and cultivation of human ectocervical epithelia cells

3.6.3.2 Seeding of hECE on filter inserts

3.6.3.3 Transepithelial electrical resistance

3.6.3.4 Permeability assessment using hECE

3.6.3.5 Limitations of primary cell cultures

3.6.4 Immortalized human cells forming monolayers (bi-/tri-layers)

3.6.4.1 Cultivation, maintenance, and permeability setup using CaSki cells

3.6.4.2 Cultivation, maintenance, and permeability setup using HEC-1A cells

3.6.4.3 Cultivation, maintenance, and permeability setup using C-33A cells

3.6.4.4 Dual-chamber model as a screening tool

3.6.5 Commercially available three-dimensional culture of nontransformed human vaginal-ectocervical epithelial cells

3.6.5.1 Need for in vitro human tissue models

3.6.5.2 EpiVaginal™ cell-based tissue model

3.6.5.3 Available EpiVaginal™ tissue types

3.6.5.4 Maintenance and use

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

3.7.3.1 Rapid removal from the eye surface

3.7.3.2 Low permeability in ocular structures

3.7.4 Ocular pharmacokinetics in the posterior segment

3.7.5 In vitro eye cellular models for drug permeability

3.7.5.1 Corneal epithelium models

3.7.5.2 Conjunctiva epithelium models

3.7.5.3 Blood-ocular barrier models

3.7.5.3.1 Blood-aqueous humor models

3.7.5.3.2 Blood-retina models

3.7.5.3.3 Retinal pigment epithelium

3.7.5.3.4 Retinal capillary endothelium

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

3.8.3.1 Two-dimensional models

3.8.3.2 Three-dimensional models

3.8.4 Reconstructed dermal equivalents

3.8.4.1 EpiSkin™

3.8.4.2 EpiDerm™

3.8.4.3 SkinEthic™

3.8.5 Reconstructed full-thickness models

3.8.5.1 StrataTest™

3.8.5.2 EpiDerm FT

3.8.5.3 EpiCS®

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

3.9.2.1 Cell types

3.9.2.2 Cell culture

3.9.2.2.1 Monoculture models

3.9.2.2.2 Co-culture models

Co-culture of ECs with glial cells/astrocytes

Co-culture of ECs with pericytes

Co-culture of ECs with other cells

3.9.2.2.3 Triple co-culture

3.9.2.3 BBB apparatus

3.9.2.3.1 Static BBB models

3.9.2.3.2 DIV models

3.9.2.3.3 Microfluidic models

3.9.3 Permeability of drugs: how to screen and study

3.9.4 Comparison of BBB models

3.9.4.1 Perfect BBB in vitro model

3.9.4.2 Qualitative 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

4.1.2.1 Harvest and preparation of porcine buccal mucosa

4.1.2.2 Transport of porcine buccal mucosa

4.1.2.3 Preservation of 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

4.2.1.1 Anatomy, histology, and physiology of the intestine.

4.2.1.2 Transport mechanisms across the intestinal mucosa

4.2.1.3 Factors governing intestinal permeability

4.2.2 Current tissue-based methodologies for intestinal permeability studies

4.2.2.1 Diffusion chambers

4.2.2.1.1 Ussing chamber

Practical aspects

Tissue preparation

Incubation buffer

Viability markers

Tissue viability

4.2.2.2 Franz cell

4.2.2.3 Everted intestinal sac

4.2.2.3.1 Practical aspects

4.2.2.4 Everted intestinal ring

4.2.2.4.1 Practical aspects

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

4.4.2.1 Nasal cavity

4.4.2.2 Tracheobronchial tree

4.4.2.3 Alveolar tissue and air-blood barrier

4.4.3 Isolated perfused lung

4.4.3.1 Lung surgical isolation and preservation

4.4.3.2 IPL as model to study absorption of compounds

4.4.3.3 Lung tissue preparation

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

4.5.3.1 Gorodeski model

4.5.3.2 EpiVaginal™ model

4.5.3.3 Other potential models

4.5.4 Ex vivo mucosal models.

4.5.4.1 General considerations for mucosal tissue handling and experimental setup.

Notes:

Description based upon print version of record.

Includes bibliographical references at the end of each chapters and index.

Description based on online resource; title from PDF title page (ebrary, viewed December 4, 2015).

ISBN:

9780081001141

0081001142