Mucoadhesive Materials and Drug Delivery Systems

Description

Mucoadhesion defined as attachment of synthetic or natural materials to mucosal tissues has been widely exploited in pharmaceutical forms. This multi-author book provides an up-to-date account of current research on mucoadhesive materials and drug delivery systems. The introductory section describes the structure and physiology of various mucosal surfaces (oral, nasal, ocular, gastrointestinal and vaginal mucosa). This is followed by chapters on the various methods used to study mucoadhesion and to characterise mucoadhesive properties of various dosage forms. The final section will summarise information on traditional and novel types of mucoadhesive materials, such as chitosan, thiomers, and liposome-based formulations.

This book is unique as there is currently no modern book considering mucoadhesion - all other existing books on the topic are either narrowly focused or more than 10 years old. Furthermore, each contributor offers specialist perspectives from a variety of global locations in both industrial and academic research centres.

Table of Contents

List of Contributors
Preface

Section One Structure and Physiology of Mucosal Surfaces in Relation to Drug Delivery 1

1 Oral Mucosa: Physiological and Physicochemical Aspects 3
Gleb E. Yakubov, Hannah Gibbins, Gordon B. Proctor and Guy H. Carpenter

• 1.1 Anatomical and Histological Aspects of Oral Cavity Tissues 3
• 1.2 Production and Composition of Saliva 8
• 1.3 Surface Architecture, Mechanical, Rheological and Transport Properties of Salivary Pellicle 16
• 1.4 Future Perspective 27
• References 27

2 Anatomy of the Eye and the Role of Ocular Mucosa in Drug Delivery 39
Peter W.J. Morrison and Vitaliy V. Khutoryanskiy

• 2.1 Introduction 39
• 2.2 Anatomy of the Eye 40
• 2.3 Introduction to Ocular Mucosa 45
• 2.4 The Role of Ocular Mucosa in Drug Delivery 47
• 2.5 Models for Ocular Drug Delivery 48
• 2.6 Recent Advances in Topical Ocular Drug Delivery 51
• 2.7 Conclusions 55
• References 55

3 Drug Delivery Across the Nasal Mucosa 61
Michelle Armstrong, Shonagh Walker, Jenifer Mains and Clive G. Wilson

• 3.1 Introduction 61
• 3.2 Drug Delivery via the Nasal Mucosa 63
• 3.3 Anatomy and Physiology of the Nasal Cavity 66
• 3.4 Disease States of the Nasal Cavity 70
• 3.5 Transport Across the Membrane 73
• 3.6 Nose-to-Brain Drug Delivery 75
• 3.7 Conclusion 76
• References 76

4 Gastrointestinal Mucosa and Mucus 83
Felipe O. Varum and Abdul W. Basit

• 4.1 Introduction 83
• 4.2 The Gastrointestinal Mucus 86
• 4.3 Conclusions 94
• References 94

5 Vaginal Mucosa and Drug Delivery 99
José das Neves, Rita Palmeira-de-Oliveira, Ana Palmeira-de-Oliveira, Francisca Rodrigues and Bruno Sarmento

• 5.1 Introduction 99
• 5.2 Drug Delivery and the Human Vagina 100
• 5.3 Vaginal Drug Dosage Forms 105
• 5.4 Novel Strategies for Enhanced Vaginal Drug Delivery 110
• 5.5 Mucoadhesion and the Vaginal Environment 111
• 5.6 Vaginal Microbicides 114
• 5.7 Users’ Acceptability and Preferences 116
• 5.8 Conclusions and Future Perspectives 118
• Acknowledgements 118
• References 119

Section Two Understanding of Mucoadhesion and Methods of Investigation 133

6 Structure and Properties of Mucins 135
Monica Berry and Anthony Corfield

• 6.1 Introduction 135
• 6.2 General Characteristics of Mucins 136
• 6.3 Mucin Glycosylation – Changes in Disease 139
• 6.4 Dynamics of Mucin Synthesis and Function 142
• 6.5 Mucin Gel Formation on Cell Surfaces 143
• 6.6 Mucin Therapeutics 148
• 6.7 Polysaccharide Coatings to Enable Probiotic Delivery 149
• 6.8 Gene Cloning and Drug Delivery 149
• 6.9 Chemo-Enzymatic Synthesis of O-Glycans for Drug Delivery 149
• 6.10 Glycan Legislation 150
• References 151

7 Theories of Mucoadhesion 159
John D. Smart

• 7.1 Introduction 159
• 7.2 Mucous Membranes 159
• 7.3 Mucoadhesives 160
• 7.4 The Adhesive Interaction 160
• 7.5 Mucoadhesion 162
• 7.6 Solid Mucoadhesion 162
• 7.7 Semi-solid Mucoadhesion 168
• 7.8 Liquid Mucoadhesion 169
• 7.9 Modified Materials 169
• 7.10 Conclusions 170
• References 170

8 Methods to Study Mucoadhesive Dosage Forms 175
Maya Davidovich-Pinhas and Havazelet Bianco-Peled

• 8.1 Introduction 175
• 8.2 Model Surfaces for Mucoadhesion Evaluation 176
• 8.3 Methods to Evaluate Mucoadhesion Dosage Form 177
• 8.4 Summary 189
• References 189

9 Methods for Assessing Mucoadhesion: The Experience of an Integrative Approach 197
Gleb E. Yakubov, Scott Singleton and Ann-Marie Williamson

• 9.1 Mucins and Mucosal Architecture 197
• 9.2 Concept of Length and Time Scales in Mucoadhesion 198
• 9.3 Experimental Approaches to Measuring Mucosal Interactions 201
• 9.4 Integrative Approaches. Layer-by-Layer Assembled Multilayers: A Tool for Studying Mucoadhesion 208
• 9.5 Future Perspective 224
• References 225

Section Three Mucoadhesive Materials 233

10 Chitosan 235
Joshua Boateng, Isaac Ayensu and Harshavardhan Pawar

• 10.1 Introduction 235
• 10.2 Material and Physicochemical Properties of Chitosan 236
• 10.3 Applications 240
• 10.4 Material Characterisation of Bioadhesive Chitosan Formulations 245
• 10.5 Summary 247
• References 247

11 Thiomers 255
Christiane Müller and Andreas Bernkop-Schnürch

• 11.1 Introduction 255
• 11.2 Thiolated Polymers 257
• 11.3 Sulfhydryl Group Contribution 260
• 11.4 Mechanism of Mucoadhesion 262
• 11.5 Mucoadhesive Properties 263
• 11.6 Additional Properties of Thiolated Polymers 264
• 11.7 Mucoadhesive Dosage Forms Based on Thiomers 267
• 11.8 Biopharmaceutical Use of Thiomers 269
• 11.9 Safety and Stability 272
• 11.10 Conclusion 273
• References 273

12 Boronate-Containing Polymers 279
Alexander E. Ivanov

• 12.1 Introduction 279
• 12.2 Fundamentals of Borate and Boronate Interactions with Monoand Oligosaccharides 280
• 12.3 Multipoint Association of BCPs with Polysaccharides 282
• 12.4 Formation of Interpolymer Complexes of BCPs with Mucin Glycoprotein 284
• 12.5 Interaction of BCPs with Animal Cells 286
• 12.6 Polymeric Mucoadhesive Materials and Devices Employing Boronate – Carbohydrate Interactions 289
• 12.7 Conclusions 291
• References 292

13 Liposome-Based Mucoadhesive Formulations 297
Kohei Tahara and Hirofumi Takeuchi

• 13.1 Introduction 297
• 13.2 Oral Administration of Surface-Modified Liposomes with the Mucoadhesive Properties 298
• 13.3 The Behaviour of Liposomes After Oral Administration 300
• 13.4 Pulmonary Administration of Peptide Drugs with Liposomal Formulations: Effective Surface Modification Using Chitosan or Poly(Vinyl Alcohol) with a Hydrophobic Anchor 301
• 13.5 Modification of Liposomes Using Mucoadhesive Polymer– Wheat Germ Agglutinin Conjugates for Pulmonary Drug Delivery 304
• 13.6 Conclusions 306
• References 306

14 Acrylated Polymers 309
Maya Davidovich-Pinhas and Havazelet Bianco-Peled

• 14.1 Introduction 309
• 14.2 Mucoadhesion 310
• 14.3 Types of Interactions Involved in the Mucoadhesion Process 310
• 14.4 Interactions Between Acrylate and Mucin Glycoprotein 311
• 14.5 Acrylated Alginate (Alginate-PEGAc) 314
• 14.6 Summary 325
• References 325

Index 329