Mucoadhesive Materials and Drug Delivery Systems

List of Contributors xv

Preface xvii

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