Advanced Drug Delivery E-Book

Ashim Mitra

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1595

Veröffentlichungsjahr: 2013

Beschreibung

Provides both fundamentals and new and emerging applications

Advanced Drug Delivery brings readers fully up to date with the state of the science, presenting the basics, formulation strategies, and therapeutic applications of advanced drug delivery. The book demonstrates how core concepts of pharmaceutical sciences, chemistry, and molecular biology can be combined and applied in order to spark novel ideas to design and develop advanced drug delivery systems for the treatment of a broad range of human diseases.

Advanced Drug Delivery features contributions from an international team of pharmaceutical scientists. Chapters reflect a thorough review and analysis of the literature as well as the authors' firsthand experience developing drug delivery systems. The book is divided into four parts:

• Part I, Introduction and Basics of Advanced Drug Delivery, explores physiological barriers, stability, transporters, and biomaterials in drug delivery
• Part II, Strategies for Advanced Drug Delivery, offers tested and proven strategies for advanced delivery of both small molecules and macromolecules
• Part III, Translational Research of Advanced Drug Delivery, focuses on regulatory considerations and translational applications of advanced drug delivery systems for the treatment of cardiovascular diseases, cancer, sexually transmitted diseases, ophthalmic diseases, and brain diseases
• Part IV, Future Applications of Advanced Drug Delivery in Emerging Research Areas, examines stem cell research, cell-based therapeutics, tissue engineering, and molecular imaging

Each chapter provides objectives and assessment questions to help readers grasp key concepts and assess their knowledge as they progress through the book.

Advanced Drug Delivery is recommended for graduates and upper-level undergraduates in the pharmaceutical sciences who need a solid foundation in the basics. It is also recommended for pharmaceutical professionals who want to take advantage of new and emerging applications in advanced drug delivery systems.

Leseprobe

Contents

Cover

Title Page

Copyright

Dedication

Preface

About the Authors

Contributors

Part I: Introduction and Basics of Advanced Drug Delivery

Chapter 1: Physiological Barriers in Advanced Drug Delivery: Gastrointestinal Barrier

1.1 Chapter Objectives

1.2 Introduction

1.3 Physiological Factors Influencing Drug Absorption

1.4 Physicochemical Factors Influencing Drug Absorption

1.5 Strategies to Overcome Gastrointestinal Barriers in Drug Delivery

1.6 Summary

Assessment Questions

References

Chapter 2: Solubility and Stability Aspects in Advanced Drug Delivery

2.1 Chapter Objectives

2.2 Solubility

2.3 Bioavailability Improvement

2.4 Stability

2.5 Summary

Assessment Questions

References

Chapter 3: The Role of Transporters and the Efflux System in Drug Delivery

3.1 Chapter Objectives

3.2 Introduction

3.3 ABC Transporters

3.4 Strategies to Overcome Active Efflux

3.5 Influx Transporters

3.6 In Vitro Models to Study Transporters

3.7 Conclusion

Assessment Questions

References

Chapter 4: Biomaterial in Advanced Drug Delivery

4.1 Chapter Objectives

4.2 Classification and Biocompatibility of Biomaterial

4.3 Bioresorbable and Bioerodible Materials

4.4 Composite Materials

4.5 Other Materials

4.6 Future Directions

Assessment Questions

References

Part II: Strategies for Advanced Drug Delivery

Chapter 5: Strategies of Drug Targeting

5.1 Chapter Objectives

5.2 Introduction

5.3 Drug Targeting Mechanisms

5.4 Delivery Systems for Drug Targeting

5.5 Ligands Used in Drug Targeting

5.6 Intracellular Targeting Strategies

5.7 Summary and Future Perspectives

Assessment Questions

References

Chapter 6: Prodrug and Bioconjugation

6.1 Chapter Objectives

6.2 Introduction and Rationale

6.3 Functional Groups for Prodrug Design

6.4 Major Objectives of Prodrug Design

6.5 Prodrugs for Improved Topical Administration (Ophthalmic and Dermal)

6.6 Prodrugs for Improved Drug Delivery to the Brain

6.7 Formulation Approaches for Sustained and Controlled Delivery of Prodrugs

6.8 Prodrugs in Clinical Trials

6.9 Conclusions and Future Perspectives

Assessment Questions

References

Chapter 7: Nanoscale Drug Delivery Systems

7.1 Chapter Objectives

7.2 Introduction

7.3 Cellular Internalization of Nanoparticulate Systems

7.4 Nanoparticles

7.5 Micelles

7.6 Liposomes

7.7 Conclusion

Assessment Questions

References

Chapter 8: Stimuli-Responsive Target Strategies

8.1 Chapter Objectives

8.2 Introduction

8.3 Physiological-Factor-Based Targeting Formulations

8.4 Magnetic Targeting Particles

8.5 Ligand-Based Targeting Formulations

8.6 Formulations Approach Based on Host Receptor Targeting

8.7 Design of a Core Shell Microparticle: AN Example of Formulation Development

Assesment Questions

References

Chapter 9: Implants

9.1 Chapter Objectives

9.2 Introduction

9.3 Polymeric Implantable Systems

9.4 Clinical and Therapeutic Applications of Polymeric Implant Systems

9.5 Implantable Pump (Mechanical) Systems

9.6 Clinical and Therapeutic Applications of Implantable Pump Systems

9.7 Clinical Application of Implants for Delivery of Narcotic Analgesics

9.8 Biocompatibility Issues of Implantable Drug Delivery Systems

9.9 Conclusion

Assessment Questions

References

Chapter 10: Aptamers in Advanced Drug Delivery

10.1 Chapter Objectives

10.2 Introduction

10.3 Aptamer Discovery Using Selex

10.4 Characteristics of Aptamers as Targeting Ligands in Drug Delivery Systems

10.5 Applications of Aptamers as Targeting Ligands in Drug Delivery

10.6 Novel Applications of Aptamers in Advanced Drug Delivery

10.7 Summary

Assessment Questions

Acknowledgments

References

Chapter 11: Nanofiber

11.1 Chapter Objectives

11.2 Introduction

11.3 Polymers for Nanofiber Preparation

11.4 Methods for Nanofiber Fabrication

11.5 Biomedical Applications

Assessment Questions

References

Chapter 12: Biomimetic Self-Assembling Nanoparticles

12.1 Chapter Objectives

12.2 Introduction

12.3 Body

12.4 Outlook Summary

Assessment Questions

References

Chapter 13: Protein and Peptide Drug Delivery

13.1 Chapter Objectives

13.2 Introduction

13.3 Challenges for Protein and Peptide Drug Delivery

13.4 Mechanism of Absorption

13.5 Strategies to Enhance Protein and Peptide Absorption

13.6 Conclusion

Assessment Questions

References

Chapter 14: Delivery of Nucleic Acids

14.1 Chapter Objectives

14.2 Introduction

14.3 Types of Nucleic Acids and Their Mechanisms

14.4 Barriers for Nucleic Acids Delivery

14.5 Strategies to Overcome the Biological Barriers

14.6 Nucleic Acid Delivery Systems

14.7 Viral Vectors

14.8 Conclusion and Future Perspectives

Assessment Questions

References

Chapter 15: Delivery of Vaccines

List of Abbreviations

15.1 Chapter Objectives

15.2 Introduction

15.3 Immunological Mechanisms

15.4 Types of Vaccines

15.5 Physicochemical Properties of Vaccine Delivery Systems

15.6 Vaccine Delivery Systems

15.7 Adjuvants (Immunopotentiators)

15.8 Route of Administration and Devices

15.9 Conclusion

Assessment Questions

References

Part III: Translational Research of Advanced Drug Delivery

Chapter 16: Regulatory Considerations and Clinical Issues in Advanced Drug Delivery

16.1 Chapter Objectives

16.2 Introduction

16.3 Modified-Release Oral Dosage Form

16.4 Sustained-Release Parenteral Dosage Forms

16.5 Lipid-Based Oral Dosage Forms

16.6 Transdermal Delivery Systems

16.7 Respiratory Drug Delivery Systems

16.8 Drug-Eluting Stents

16.9 Nanotechnology-Derived Drug Delivery Systems

16.10 Nucleic Acid Therapeutics

Assessment Questions

References

Chapter 17: Advanced Drug Delivery in Cancer Therapy

17.1 Chapter Objectives

17.2 Introduction

17.3 Biological Characteristics of Cancer

17.4 Drug Delivery to Cancer Cells by Nanoscale Carriers

17.5 Drug Delivery to Cancer Cells by Bioconjugates

17.6 Drug Delivery to Cancer by Gel Systerms

17.7 Conclusion and Future Perspecives

Assessment Questions

References

Chapter 18: Advanced Delivery in Cardiovascular Diseases

18.1 Chapter Objectives

18.2 Cardiovascular System

18.3 The Function of Heart Valves

18.4 The Structure of Heart Valves

18.5 Heart Valve Dysfunction

18.6 Bioprosthetic Heart Valve Failure

18.7 Tissue Engineering in Heart Valves

Assessment Questions

References

Chapter 19: Recent Advances in Ocular Drug Delivery

19.1 Chapter Objectives

19.2 Introduction

19.3 Barriers to Ocular Drug Delivery

19.4 Advances in Ocular Drug Delivery

19.5 Controled Drug Delivery

19.6 Macromolecular Drug Delivery

19.7 Stem-Cell-Based Drug Delivery System

19.8 Conclusion

Assessment Questions

References

Chapter 20: Advanced Drug Delivery Against STD

20.1 Chapter Objectives

20.2 Introduction

20.3 Physiology of Vagina

20.4 Std and Prevention Strategies

20.5 Vaginal Delivery Systems Against STDs

20.6 Drug Release and Efficacy Studies of Vaginal Formulations

20.7 Testing of Biocompatibility of the Vaginal Systems

20.8 Conclusion

Assesment Questions

References

Chapter 21: Advanced Drug Delivery to the Brain

21.1 Chapter Objectives

21.2 Introduction

21.3 Barriers for Brain Drug Delivery

21.4 Direct Systemic Delivery

21.5 Direct CNS Delivery

21.6 Chemical and Physiological Approaches

21.7 Conclusion

Assessment Questions

References

Part IV: Future Applications of Advanced Drug Delivery in Emerging Research Areas

Chapter 22: Cell-Based Therapeutics

22.1 Chapter Objectives

22.2 Introduction

22.3 Bone Marrow Transplantation as a Prototype of Cell-Based Therapeutics

22.4 Cells—Active Pharmaceutical Ingredients of Cell-Based Therapeutics

22.5 Typical Examples for Disease-Specific Applications

22.6 Brief Overview on Human Case Studies

22.7 Pharmaceutical Considerations on Cell-Based Therapeutics

22.8 Conclusion and Future Perspectives

Assessment Questions

References

Chapter 23: Biomedical Applications and Tissue Engineering of Collagen

23.1 Chapter Objectives

23.2 Introduction

23.3 Characterization of Collagen as a Biomaterial

23.4 Collagen-Based Drug Delivery Systems

23.5 Collagen-Based Systems for Gene Delivery

23.6 Collagen-Based Systems for Tissue Engineering

23.7 Collagen Film as a Calcifiable Matrix System: an Example of the Formulation Development

23.8 Conclusion

Assesment Questions

References

Chapter 24: Molecular Imaging of Drug Delivery

24.1 Chapter Objectives

24.2 Introduction

24.3 Imaging Modalities

24.4 Molecular Imaging of Drug Delivery

24.5 Imaging Therapeutic Efficacy of Drug Delivery Systems

24.6 Theranostics

24.7 Summary

Assessment Questions

References

Answers

Index

Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey.

Published simultaneously in Canada.

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Library of Congress Cataloging-in-Publication Data:

Advanced drug delivery/edited by Ashim K. Mitra, Chi H. Lee, Kun Cheng.

p.; cm.

Includes bibliographical references and index.

ISBN 978-1-118-02266-5 (cloth)

I. Mitra, Ashim K., 1954- II. Lee, Chi H. (Professor) III. Cheng, Kun (Professor)

[DNLM: 1. Drug Delivery Systems. QV 785]

RM301.12

615.1–dc23

2013014003

I would like to dedicate this book to the pharmaceutical industry.

Ashim K. Mitra

I owe my deepest gratitude to my wife, Dr. Yugyung Lee, for her love, devotion, and enormous support. I am pleased to mention my children, Eddie and Jason, who have given me encouragement and endless challenge.

Chi H. Lee

I dedicate this book to my parents, Mr. Guangxiong Cheng and Mrs. Pingqing Xu; my wife Lizhi Sun; my children Daniel and Jessica for their love and continuous support; and my mentors who have inspired me to pursue a career in science.

Kun Cheng

Preface

During the past four decades, we have witnessed unprecedented breakthroughs in advanced delivery systems for efficient delivery of various therapeutic agents including small molecules as well as macromolecules. The development of advanced drug delivery systems for small-molecule drugs not only improves drug efficacy but also opens up new markets for the pharmaceutical industry. The global market for advanced drug delivery systems is expected to increase to $196.4 billion through 2014. On the other hand, remarkable progresses in molecular biology and biotechnology over the past two decades have not been matched by progresses in efficient delivery systems for the improvement of therapeutic efficacy. Therefore, it is integral to transform our knowledge in molecular biology and biotechnology into the development of effective delivery systems for macromolecular therapeutics.

Advanced Drug Delivery aims to provide up-to-date information of the basics, formulation strategies, and various therapeutic applications of advanced drug delivery. The goal of this book is to teach the philosophy of how to articulate practically the concepts of pharmaceutical sciences, chemistry, and molecular biology in such an integrated way that can ignite novel ideas to design and develop advanced delivery systems against various diseases.

This book is divided into four parts, starting with fundamentals related to physiological barriers, stability, transporters, and biomaterials in drug delivery. Then, it moves on to discuss different strategies that have been used for advanced delivery of small molecules as well as macromolecules. The third part focuses on regulatory considerations and translational applications of various advanced drug delivery systems in the treatment of critical and life-threatening diseases, such as cardiovascular diseases, cancer, sexually transmitted diseases, ophthalmic diseases, and brain diseases. The book ends with the applications of advance drug delivery in emerging research fields, such as stem cell research, cell-based therapeutics, tissue engineering, and molecular imaging. Each chapter provides objectives and assessment questions to facilitate student learning.

According to the report from the American Association of Pharmaceutical Scientists (AAPS), there is a critical shortage of well-trained pharmaceutical scientists in the areas of product development and related pharmaceutical technologies. We hope that this book will serve as a valuable tool not only for pharmacy graduate and undergraduate students but also for those healthcare professionals who have no pharmacy background but are engaged with drug development.

Finally, we would like to express our sincere appreciation and gratitude to all the contributors who spent enormous effort to share their knowledge and expertise in multiple aspects of advanced drug delivery.

Ashim K. Mitra

Chi H. Lee

Kun Cheng

About the Authors

Ashim K. Mitra received his Ph.D. in pharmaceutical chemistry in 1983 from the University of Kansas. He joined the University of Missouri—Kansas City (UMKC) in 1994 as chairman of the Pharmaceutical Sciences Department. He is currently the Vice Provost for Interdisciplinary Research, the UMKC Curators' Professor of Pharmacy, and a co-director of the Vision Research Center, UMKC School of Medicine. He has more than 30 years of experience in the field of ocular drug delivery and disposition. He has authored and co-authored over 280 refereed articles and 60 book chapters in the area of formulation development and ocular drug delivery; he has been awarded 9 patents and has presented (along with his research group) well over 500 presentations/abstracts at national and international scientific meetings. Prof. Mitra's work has attracted over US$6 million in funding from government agencies such as the National Institutes of Health (NIH), Department of Defense (DOD), and pharmaceutical companies. He is the recipient of numerous research awards from NIH, AAPS, AACP, ARVO, and pharmaceutical organizations.

Chi H. Lee received his B.S. degree in pharmacy from Seoul National University, South Korea. After getting his M.S. degree at the University of Washington, Seattle, he attended Rutgers University, North Brunswick, NJ, where he earned his Ph.D. degree. He completed his postdoctoral training at the University of Michigan Medical Center, Ann Arbor.

Prof. Lee was previously a member of the faculty at the University of Louisiana, Monroe, College of Pharmacy, before he moved to the University of Missouri—Kansas City, where his responsibilities include teaching undergraduate and graduate pharmacy students.

Prof. Lee has been actively involved in pharmaceutical research for more than three decades and has a special interest in the areas of formulation development and pathological mechanisms on microbicidal and cardiovascular devices and polymer-based systems. He has authored more than 55 articles and three book chapters on those subjects, and he has delivered more than 200 scientific presentations at local, national, and international symposia. Prof. Lee has received grants from various funding agencies including the National Institutes of Health (NIH) and the American Heart Association. He has served as a member of the American Association of Pharmaceutical Scientists, Society for Biomaterials, American Association of College of Pharmacy, Controlled Release Society, and American Heart Association.

Kun Cheng is an associate professor of pharmaceutical sciences at the University of Missouri—Kansas City (UMKC). He received his B.S. and M.S. degrees in pharmaceutical sciences from China Pharmaceutical University. He also received an M.S. degree in pharmacy from the National University of Singapore. He worked at the Bright Future Pharmaceutical Company in Hong Kong prior to joining the University of Tennessee Health Science Center, where he received his Ph.D. in pharmaceutical sciences. His current research focuses on the development of novel drug delivery systems for siRNA and small-molecule drugs. Much of the effort from his laboratory has dealt with the therapeutic exploration of macromolecular agents, which have poor stability and inefficient cellular uptake.

Prof. Cheng has been actively engaged in extramural professional activities and in teaching graduate and PharmD students. He has edited one book titled Advanced Delivery and Therapeutic Applications of RNAi and two theme issues for the journals Molecular Pharmaceutics and Pharmaceutical Research. He is the recipient of the 2011 American Association of Pharmaceutical Scientists (AAPS) New Investigator Grant Award in Pharmaceutics and Pharmaceutical Technologies.

Contributors

Gayathri Acharya, University of Missouri—Kansas City, Kansas City, MO, USA

Vibhuti Agrahari, University of Missouri—Kansas City, Kansas City, MO, USA

Megha Barot, University of Missouri—Kansas City, Kansas City, MO, USA

Haibo Cai, East China University of Science and Technology, Shanghai, China

Mei-Ling Chen, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA

Zhijin Chen, University of Missouri—Kansas City, Kansas City, MO, USA

Kun Cheng, Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri—Kansas City, Kansas City, MO, USA

Hoo-Kyun Choi, School of Pharmacy, Chosun University, Gwangju, South Korea

Kishore Cholkar, University of Missouri—Kansas City, Kansas City, MO, USA

Hari R. Desu, Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA

Omid C. Farokhzad, Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

Weiwei Gao, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

Mitan R. Gokulgandhi, University of Missouri—Kansas City, Kansas City, MO, USA

Nazila Kamaly, Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

Varun Khurana, University of Missouri—Kansas City, Kansas City, MO, USA

Deep Kwatra, Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA

Chi H. Lee, Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri—Kansas City, Kansas City, MO, USA

Yugyung Lee, School of Interdisciplinary Computing and Engineering, University of Missouri—Kansas City, Kansas City, MO, USA

Zheng-Rong Lu, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

Rubi Mahato, University of Missouri—Kansas City, Kansas City, MO, USA

Nanda K. Mandava, University of Missouri—Kansas City, Kansas City, MO, USA

Mukul Minocha, University of Missouri—Kansas City, Kansas City, MO, USA

Ashim K. Mitra, Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri—Kansas City, Kansas City, MO, USA

Mridul Mukherji, University of Missouri—Kansas City, Kansas City, MO, USA

D. Alexander Oh, Clinical Pharmacology Akros Pharma, Inc., Princeton, NJ

Dhananjay Pal, University of Missouri—Kansas City, Kansas City, MO, USA

Ashaben Patel, University of Missouri—Kansas City, Kansas City, MO, USA

Mitesh Patel, University of Missouri—Kansas City, Kansas City, MO, USA

Durga Paturi, University of Missouri—Kansas City, Kansas City, MO, USA

Bin Qin, University of Missouri—Kansas City, Kansas City, MO, USA

Animikh Ray, University of Missouri—Kansas City, Kansas City, MO, USA

Jwala Renukuntla, University of Missouri—Kansas City, Kansas City, MO, USA

Maxim G. Ryadnov, National Physical Laboratory, Teddington, Middlesex, UK

Sujay Shah, University of Missouri—Kansas City, Kansas City, MO, USA

Ravi S. Shukla, University of Missouri—Kansas City, Kansas City, MO, USA

Robhash K. Subedi, College of Pharmacy, Chosun University, Gwangju, South Korea

Wanyi Tai, University of Missouri—Kansas City, Kansas City, MO, USA

Wen-Song Tan, East China University of Science and Technology, Shanghai, China

Laura A. Thoma, Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA

Ramya Krishna Vadlapatla, University of Missouri—Kansas City, Kansas City, MO, USA

Aswani Dutt Vadlapudi, University of Missouri—Kansas City, Kansas City, MO, USA

Divya Teja Vavilala, University of Missouri—Kansas City, Kansas City, MO, USA

Shaoying Wang, University of Missouri—Kansas City, Kansas City, MO, USA

Wuchen Wang, University of Missouri—Kansas City, Kansas City, MO, USA

Xiaoyan Yang, University of Missouri—Kansas City, Kansas City, MO, USA

Zhaoyang Ye, The State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, China

Yan Zhou, East China University of Science and Technology, Shanghai, China

Part I

Introduction and Basics of Advanced Drug Delivery

1

Physiological Barriers in Advanced Drug Delivery: Gastrointestinal Barrier

D. Alexander Oh and Chi H. Lee

1.1 Chapter objectives

1.2 Introduction

1.3 Physiological factors influencing drug absorption

1.4 Physicochemical factors influencing drug absorption

1.5 Strategies to overcome gastrointestinal barriers in drug delivery

1.6 Summary

Assessment questions

References

1.1 Chapter Objectives

To outline gastrointestinal anatomy and physiology impacting advanced oral drug delivery systems.To review key physiological and physicochemical factors influencing drug absorption.To illustrate efficient strategies for overcoming gastrointestinal barriers in drug delivery.

1.2 Introduction

Drug delivery through oral administration is a complicated process: A drug must withstand the digestive processes and penetrate through the gastrointestinal (GI) barrier into the bloodstream. Drugs absorbed from the GI tract travel through portal veins to the liver, and then they are subjected to first-pass metabolism by the hepatic enzymes before entering the systemic circulation [1]. The oral route of drug administration is traditionally known as the most preferred route for systemic drug delivery, even though there are disadvantages, such as unpredictable and erratic absorption, gastrointestinal intolerance, incomplete absorption, degradation of drug in GI contents, and presystemic metabolism, mostly resulting in reduced bioavailability.

The primary functions of the GI tract are absorption and digestion of food, as well as secretion of various enzymes or fluids [2]. The gastrointestinal mucosa forms a barrier between the body and a luminal environment that contains not only nutrients but also potentially hostile microorganisms and toxins. The normal function of the GI barrier, which is referred to the properties of the gastric and intestinal mucosa, is essential for disease prevention and overall maintenance of health. The major challenge in drug delivery through the GI tract is to achieve efficient transport of nutrients and drugs across the epithelium while rigorously excluding passage of harmful molecules and organisms into the body.

The performance of GI barriers to drug transport may largely depend on the physicochemical characteristics of drugs. Water-soluble small molecules may not be easily absorbed unless a specific transporter to those molecules is present, while lipophilic drugs can be relatively well absorbed through GI barriers. Mucosal transporters include PEPT, OATP, OCT, MCT, ASBT, MDR1, MRP, and BCRP among others [3] as shown in Figure 1.1. Large-molecule drugs, such as antibodies and proteins, may suffer extensive enzymatic degradation in the GI tract [4].

Figure 1.1 The intestinal metabolizing enzymes and uptake/efflux transporters [3].

In this chapter, gastrointestinal mucous membranes and gut physiology will be intensively covered from the perspective of physiological barriers, which will lead to thorough understanding of key obstacles to advanced oral drug delivery.

1.2.1 Anatomy of Gastrointestinal Tract

1.2.1.1 Gastrointestinal Anatomy

The major components of the gastrointestinal tract are the stomach, small intestine, and large intestine. The small intestine with a length of about 6 m includes the duodenum, jejunum, and ileum [5]. The stomach is a pouch-like structure lined with a relatively smooth epithelial surface. Extensive absorption of numerous weakly acidic or nonionized drugs and certain weakly basic drugs were demonstrated in the stomach under varying experimental conditions [2,6,7].

The small intestine is the most important site for drug absorption in the gastrointestinal tract. The epithelial surface area through which absorption of drug takes place in the small intestine is enormously large because of the presence of villi and microvilli, finger-like projections arising from and forming folds in the intestinal mucosa as shown in [8]. The surface area decreases sharply from proximal to distal small intestine and was estimated to range from 80-cm/cm serosal length just beyond the duodeno-jejunal flexure to about 20-cm/cm serosal length just before the ileo-cecal valve in humans [9]. The total surface area of the human small intestine is about 200 to 500 m [6,7]. The small intestine is made up of various types of epithelial cells, i.e., absorptive cells (enterocytes), undifferentiated crypt cells, goblet cells, endocrine cells, paneth cells, and M cells. There is also a progressive decrease in the average size of aqueous pores from proximal to distal small intestine and colon [10,11].