Preface xvii Part 1: Fundamental Aspects 1 1 Introduction, Theories and Mechanisms of Bioadhesion 3 Kamla Pathak and Rishabha Malviya 1.1 Introduction 4 1.1.1 Historical Perspective 4 1.1.2 Bioadhesion in Biological Systems 5 1.1.3 Bioadhesive/Mucoadhesive 6 1.

1.4 Factors Affecting Mucoadhesion 6 1.1.4.1 Molecular Weight of Polymer 6 1.1.4.2 Concentration of Polymer Used 7 1.

1.4.3 Flexibility of Polymer Chains 7 1.1.4.4 Swelling 7 1.1.4.

5 pH at Polymer-Mucus Interface 7 1.1.4.6 Mucin Turnover Rate 7 1.1.4.7 Stereochemistry 7 1.2 Bioadhesive Interactions 8 1.

3 The Mechanistic Approach to Bioadhesion 9 1.4 Factors Controlling Bioadhesion 10 1.4.1 Chemical Interactions 10 1.4.1.1 Mussel Adhesion 10 1.4.

1.2 Cell Adhesion to Biomaterials 11 1.4.2 Surface Morphology Effects 11 1.4.3 Physiological Factors 12 1.4.4 Physical and Mechanical Factors 12 1.

4.4.1 Wetting Phenomenon 12 1.4.4.2 Interpenetration 12 1.5 Theories of Bioadhesion 13 1.5.

1 Wetting Theory 13 1.5.2 Diffusion Theory 15 1.5.3 Electronic Theory 16 1.5.4 Adsorption Theory 16 1 . 5.

5 Fracture Theory 16 1.6 Stages of Mucoadhesion 17 1.7 Modulation of Mucoadhesion 18 1.8 Adhesion Promoters 19 1.9 Surface Free Energy Analysis of Bioadhesion 19 1.10 Molecular Biology in Bioadhesion 20 1.11 Bioadhesives from Marine Sources 21 1.12 Mucoadhesive Drug Delivery Systems 22 1.

13 Summary 23 References 23 2 Bioadhesive Polymers for Drug Delivery Applications 29 Kenneth Chinedu Ugoeze 2.1 Introduction 30 2.1.1 Drug Delivery 30 2.2 Bioadhesive/Mucoadhesive Drug Delivery Systems 31 2.2.1 Some Advantages of Bioadhesive/Mucoadhesive Drug Delivery Systems 32 2.2.

2 The General Need for Bioadhesive/Mucoadhesive Drug Delivery Systems 33 2.3 Mechanism of Bioadhesion 33 2.4 Requirements for an Ideal Bioadhesive/Mucoadhesive Polymer 34 2.5 Factors Affecting Bioadhesion/Mucoadhesion 35 2.5.1 Polymer Related Factors 35 2.5.1.

1 Molecular Weight 36 2.5.1.2 Chain Length 36 2.5.1.3 Flexibility 36 2.5.

1.4 Cross-Linking 36 2.5.1.5 Presence of Functional Groups 37 2.5.1.6 Concentration of Active Polymer 37 2.

5.2 Environmental Factors 37 2.5.2.1 pH and Charge on the Polymer 38 2.5.2.2 Degree of Hydration 38 2.

5.2.3 Initial Contact Time 38 2.5.2.4 Applied Pressure 38 2.5.2.

5 Swelling 39 2.5.2.6 Ionic Strength 39 2.5.2.7 Mucus Gel Viscosity 39 2.5.

3 Physiological Factors 39 2.5.3.1 Mucin Turnover 39 2.5.3.2 Disease States 39 2.6 Bioadhesive Polymers for Drug Delivery Applications 40 2.

6.1 Polymers 40 2.6.1.1 Natural Polymers 40 2.6.1.2 Synthetic Polymers 40 2.

6.2 Bioadhesive/Mucoadhesive Polymers 40 2.6.3 Classification of Mucoadhesive Polymers 41 2.6.3.1 Classification Based on the Origin of the Polymer 41 2.6.

3.2 Classification Based on Aqueous Solubility of the Polymer 41 2.6.3.3 Classification Based on the Type of Charge on the Polymer 42 2.6.4 Natural Polymers 42 2.6.

4.1 Chitosan 42 2.6.4.2 Starch 43 2.6.4.3 Gelatin 44 2.

6.4.4 Alginates 44 2.6.4.5 Hyaluronic Acid 45 2.6.5 Synthetic Polymers 45 2.

6.5.1 Cellulose Derivatives 45 2.6.5.2 Polyacrylates 46 2.6.5.

3 Poly (ethylene glycol) (PEG) 46 2.6.6 Classification Based on Aqueous Solubility of the Polymer 46 2.6.6.1 Water-Soluble Polymers 46 2.6.6.

2 Water-Insoluble Polymers 46 2.6.7 Classification Based on the Type of Charge on the Polymer 47 2.6.7.1 Cationic Polymers 47 2.6.7.

2 Anionic Polymers 47 2.6.7.3 Non-Ionic Polymers 47 2.7 Prospects of Bioadhesive/Mucoadhesive Polymers in Bioadhesive Drug Delivery 47 2.8 Summary 48 Acknowledgements 49 References 49 3 In Vitro , Ex Vivo and In Vivo Methods for Characterization of Bioadhesiveness of Drug Delivery Systems 57 Ljiljana Djekic and Martina Martinovic 3.1 Introduction 58 3.2 Mechanisms of Bioadhesion 59 3.

3 Bioadhesive Drug Delivery Systems (BDDS) 62 3.3.1 BDDS for Cutaneous Application 62 3.3.2 BDDS for Buccal Application 63 3.3.3 BDDS for Peroral Application 64 3.3.

4 BDDS for Vaginal Application 65 3.3.5 BDDS for Nasal Application 66 3.3.6 BDDS for Ocular Application 67 3.4 Methods for Testing Bioadhesive Property of BDDS 68 3.4.1 In Vitro/Ex Vivo Tests 68 3.

4.1.1 Bioadhesion Strength Tests 68 3.4.1.2 In Vitro Methods for Characterization of Bioadhesion at the Molecular Level 81 3.4.2 In Vivo Methods 85 3.

4.2.1 Radiolabelled BDDS Transit Studies 86 3.4.2.2 Gamma Scintigraphy 87 3.4.2.

3 In Vivo Detachment Tests 87 3.5 Summary 89 References 90 Part 2: Bioadhesive Formulations 99 4 Bioadhesive Films for Drug Delivery Systems 101 Kampanart Huanbutta and Tanikan Sangnim 4.1 Introduction 101 4.2 Theories of Bioadhesion 102 4.3 Bioadhesive Film-Forming Agents 103 4.4 Drug Delivery Applications of Bioadhesive Films 105 4.4.1 Topical and Transdermal Drug Delivery 105 4.

4.1.1 Patches 105 4.4.1.2 Film-Forming Systems 106 4.4.2 Mucosal Drug Delivery 106 4.

4.2.1 Buccal Drug Delivery 106 4.4.2.2 Vaginal Drug Delivery 107 4.4.2.

3 Rectal Drug Delivery 107 4.4.2.4 Ocular Drug Delivery 108 4.4.2.5 Nasal Drug Delivery 109 4.4.

3 Oral Drug Delivery 109 4.4.3.1 Orodispersible Films (ODFs) 109 4.4.3.2 Sublingual Films 110 4.4.

3.3 Oral Colon-Specific Drug Delivery 110 4.5 Current and Novel Bioadhesive Film Fabrication Techniques 111 4.5.1 Solvent Casting 111 4.5.2 Extrusion 111 4.5.

3 Rolling 111 4.5.4 2D Printing 112 4.6 Evaluation of Bioadhesive Films 113 4.6.1 Bioadhesive Strength 113 4.6.2 Tensile Strength Measurement 114 4.

6.3 Morphology and Thickness 114 4.6.4 Moisture Content 114 4.6.5 Permeation 115 4.6.6 Swelling 116 4.

6.7 Irritation 116 4.6.8 Stability 116 4.6.9 Drug Loading and Drug Entrapment Efficiency 117 4.7 Summary 117 4.8 Acknowledgements 118 References 118 5 Redox-Responsive Disulphide Bioadhesive Polymeric Nanoparticles for Colon-Targeted Drug Delivery 123 Erazuliana Abd Kadir and Vuanghao Lim 5.

1 Introduction 123 5.2 Mechanism of Disulphide Bond Formation 124 5.3 Disulphide Polymers for Colon Drug Delivery 125 5.4 Colon-Targeted Drug Delivery (CTDD) 126 5.4.1 Condition of the Colon for Drug Delivery 127 5 . 4.2 Approaches for Colon Drug Delivery 128 5.

4.3 Limitations of CTDD 129 5.5 Nanoformulations of Disulphide Polymers 130 5.5.1 Thiolated Pectin Polymers 130 5.5.2 Thiolated Sodium Alginate (TSA) Polymers 131 5.5.

3 Thiolated Chitosan (TCS) Polymers 134 5.5.4 Thiolated Hyaluronic Acid Polymers 136 5.5.5 Thiolated Dextran Polymers 137 5.5.6 Other Thiolated Polymers 138 5.6 Summary 140 Acknowledgements 140 References 140 6 Bioadhesive Hydrogels and Their Applications 147 Hitesh Chopra, Sandeep Kumar and Inderbir Singh 6.

1 Introduction 147 6.1.1 Bioadhesive Polymer 148 6.1.2 Hydrogels 150 6.1.3 Bioadhesive Hydrogels 155 6.2 Bioadhesive Hydrogel Films 155 6.

3 Bioadhesive Hydrogels for Gastrointestinal Delivery 156 6.4 Bioadhesive Hydrogels Administered through Injection 156 6.5 Bioadhesive Hydrogels for Vaginal Delivery 159 6.6 Bioadhesive Hydrogels for Rectal Delivery 160 6.7 Mucoadhesive Hydrogels Based Nanoparticles 161 6.8 Patents and Future Perspectives 161 6.9 Summary 164 References 164 Part 3: Drug Delivery Applications 171 7 Ocular Bioadhesive Drug Delivery Systems and Their Applications 173 Anju Sharma, Mukesh S. Patil, Pravin Pawar, A.

A. Shirkhedkar and Inderbir Singh 7.1 Introduction 174 7.2 Anatomy and Physiology of the Eye 175 7.2.1 Anatomy and Function of the Eye 175 7.2.2 Structure of Cornea 176 7.

3 Various Bioadhesive/Mucoadhesive Polymers for Ocular Delivery 176 7.3.1 Chitosan as Ocular Bioadhesive 177 7.3.2 Starch (Drum-Dried Waxy Maize Starch, Pregelatinized Starch) 180 7.3.3 Sodium Hyaluronate (SH) as Ocular Bioadhesive 181 7.3.

3.1 Functions of Sodium Hyaluronate 181 7.3.3.2 Viscoelasticity 182 7.3.3.3 Contact Angle 182 7.

3.3.4 Adherence to the Mucin Layer (Mucoadhesivity) 183 7.3.3.5 Water Retention 184 7.3.3.

6 Healing of Superficial Keratitis 184 7.3.3.7 Free Radical Scavenging 184 7.3.4 Alginate Based Ocular Bioadhesive 184 7.3.4.

1 General Properties of ALGs 185 7.3.5 Gellan Gum as Ocular Bioadhesive 188 7.3.6 Albumin 189 7.3.7 Collagen Based Ocular Bioadhesive 190 7.3.

8 Xanthan Gum 192 7.3.9 Guar Gum 193 7.3.10 Gelatin 193 7.3.11 Tamarind Seed Polysaccharide (Xyloglucan) 195 7.3.

12 Arabinogalactan 196 7.3.13 Gum Cordia 197 7.3.14 Bletilla Striata Polysaccharide (BSP) 197 7.3.15 Locust Bean Gum (Carob Bean Gum) 198 7.3.

16 Carrageenan 198 7.4 Summary 199 Re.