Mucoadhesive Materials and Drug Delivery Systems

Dr Vitaliy Khutoryanskiy is a Reader in Pharmaceutical Materials at the Reading School of Pharmacy, the University of Reading, UK. His expertise is on water-soluble polymers and hydrogels, mucoadhesive polymeric materials, stimuli-responsive polymers and polymeric nanomaterials. Khutoryanskiy has taught modules in Dosage Form Design and Advanced Pharmaceutics to MPharm students for the past 5 years, as well as being invited to give talks relating to mucoadhesion at various universities, companies and scientific conferences. He has written 79 peer reviewed papers, 6 reviews, 3 book chapters, 1 edited book, and 2 patent applications. Prior to joining the University of Reading he worked as a postdoctoral researcher and lecturer at many universities including the Kazakh National Technical University, Khazakhstan, where he received a PhD in polymer chemistry.

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 Jose 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 Muller and Andreas Bernkop-Schnurch 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