Preface xviiPart 1: Fundamental Aspects 11 Introduction, Theories and Mechanisms of Bioadhesion 3Kamla Pathak and Rishabha Malviya1.1 Introduction 41.1.1 Historical Perspective 41.1.2 Bioadhesion in Biological Systems 51.1.3 Bioadhesive/Mucoadhesive 61.1.4 Factors Affecting Mucoadhesion 61.1.4.1 Molecular Weight of Polymer 61.1.4.2 Concentration of Polymer Used 71.1.4.3 Flexibility of Polymer Chains 71.1.4.4 Swelling 71.1.4.5 pH at Polymer-Mucus Interface 71.1.4.6 Mucin Turnover Rate 71.1.4.7 Stereochemistry 71.2 Bioadhesive Interactions 81.3 The Mechanistic Approach to Bioadhesion 91.4 Factors Controlling Bioadhesion 101.4.1 Chemical Interactions 101.4.1.1 Mussel Adhesion 101.4.1.2 Cell Adhesion to Biomaterials 111.4.2 Surface Morphology Effects 111.4.3 Physiological Factors 121.4.4 Physical and Mechanical Factors 121.4.4.1 Wetting Phenomenon 121.4.4.2 Interpenetration 121.5 Theories of Bioadhesion 131.5.1 Wetting Theory 131.5.2 Diffusion Theory 151.5.3 Electronic Theory 161.5.4 Adsorption Theory 161.5.5 Fracture Theory 161.6 Stages of Mucoadhesion 171.7 Modulation of Mucoadhesion 181.8 Adhesion Promoters 191.9 Surface Free Energy Analysis of Bioadhesion 191.10 Molecular Biology in Bioadhesion 201.11 Bioadhesives from Marine Sources 211.12 Mucoadhesive Drug Delivery Systems 221.13 Summary 23References 232 Bioadhesive Polymers for Drug Delivery Applications 29Kenneth Chinedu Ugoeze2.1 Introduction 302.1.1 Drug Delivery 302.2 Bioadhesive/Mucoadhesive Drug Delivery Systems 312.2.1 Some Advantages of Bioadhesive/Mucoadhesive Drug Delivery Systems 322.2.2 The General Need for Bioadhesive/Mucoadhesive Drug Delivery Systems 332.3 Mechanism of Bioadhesion 332.4 Requirements for an Ideal Bioadhesive/Mucoadhesive Polymer 342.5 Factors Affecting Bioadhesion/Mucoadhesion 352.5.1 Polymer Related Factors 352.5.1.1 Molecular Weight 362.5.1.2 Chain Length 362.5.1.3 Flexibility 362.5.1.4 Cross-Linking 362.5.1.5 Presence of Functional Groups 372.5.1.6 Concentration of Active Polymer 372.5.2 Environmental Factors 372.5.2.1 pH and Charge on the Polymer 382.5.2.2 Degree of Hydration 382.5.2.3 Initial Contact Time 382.5.2.4 Applied Pressure 382.5.2.5 Swelling 392.5.2.6 Ionic Strength 392.5.2.7 Mucus Gel Viscosity 392.5.3 Physiological Factors 392.5.3.1 Mucin Turnover 392.5.3.2 Disease States 392.6 Bioadhesive Polymers for Drug Delivery Applications 402.6.1 Polymers 402.6.1.1 Natural Polymers 402.6.1.2 Synthetic Polymers 402.6.2 Bioadhesive/Mucoadhesive Polymers 402.6.3 Classification of Mucoadhesive Polymers 412.6.3.1 Classification Based on the Origin of the Polymer 412.6.3.2 Classification Based on Aqueous Solubility of the Polymer 412.6.3.3 Classification Based on the Type of Charge on the Polymer 422.6.4 Natural Polymers 422.6.4.1 Chitosan 422.6.4.2 Starch 432.6.4.3 Gelatin 442.6.4.4 Alginates 442.6.4.5 Hyaluronic Acid 452.6.5 Synthetic Polymers 452.6.5.1 Cellulose Derivatives 452.6.5.2 Polyacrylates 462.6.5.3 Poly (ethylene glycol) (PEG) 462.6.6 Classification Based on Aqueous Solubility of the Polymer 462.6.6.1 Water-Soluble Polymers 462.6.6.2 Water-Insoluble Polymers 462.6.7 Classification Based on the Type of Charge on the Polymer 472.6.7.1 Cationic Polymers 472.6.7.2 Anionic Polymers 472.6.7.3 Non-Ionic Polymers 472.7 Prospects of Bioadhesive/Mucoadhesive Polymers in Bioadhesive Drug Delivery 472.8 Summary 48Acknowledgements 49References 493 In Vitro, Ex Vivo and In Vivo Methods for Characterization of Bioadhesiveness of Drug Delivery Systems 57Ljiljana Djekic and Martina Martinovic3.1 Introduction 583.2 Mechanisms of Bioadhesion 593.3 Bioadhesive Drug Delivery Systems (BDDS) 623.3.1 BDDS for Cutaneous Application 623.3.2 BDDS for Buccal Application 633.3.3 BDDS for Peroral Application 643.3.4 BDDS for Vaginal Application 653.3.5 BDDS for Nasal Application 663.3.6 BDDS for Ocular Application 673.4 Methods for Testing Bioadhesive Property of BDDS 683.4.1 In Vitro/Ex Vivo Tests 683.4.1.1 Bioadhesion Strength Tests 683.4.1.2 In Vitro Methods for Characterization of Bioadhesion at the Molecular Level 813.4.2 In Vivo Methods 853.4.2.1 Radiolabelled BDDS Transit Studies 863.4.2.2 Gamma Scintigraphy 873.4.2.3 In Vivo Detachment Tests 873.5 Summary 89References 90Part 2: Bioadhesive Formulations 994 Bioadhesive Films for Drug Delivery Systems 101Kampanart Huanbutta and Tanikan Sangnim4.1 Introduction 1014.2 Theories of Bioadhesion 1024.3 Bioadhesive Film-Forming Agents 1034.4 Drug Delivery Applications of Bioadhesive Films 1054.4.1 Topical and Transdermal Drug Delivery 1054.4.1.1 Patches 1054.4.1.2 Film-Forming Systems 1064.4.2 Mucosal Drug Delivery 1064.4.2.1 Buccal Drug Delivery 1064.4.2.2 Vaginal Drug Delivery 1074.4.2.3 Rectal Drug Delivery 1074.4.2.4 Ocular Drug Delivery 1084.4.2.5 Nasal Drug Delivery 1094.4.3 Oral Drug Delivery 1094.4.3.1 Orodispersible Films (ODFs) 1094.4.3.2 Sublingual Films 1104.4.3.3 Oral Colon-Specific Drug Delivery 1104.5 Current and Novel Bioadhesive Film Fabrication Techniques 1114.5.1 Solvent Casting 1114.5.2 Extrusion 1114.5.3 Rolling 1114.5.4 2D Printing 1124.6 Evaluation of Bioadhesive Films 1134.6.1 Bioadhesive Strength 1134.6.2 Tensile Strength Measurement 1144.6.3 Morphology and Thickness 1144.6.4 Moisture Content 1144.6.5 Permeation 1154.6.6 Swelling 1164.6.7 Irritation 1164.6.8 Stability 1164.6.9 Drug Loading and Drug Entrapment Efficiency 1174.7 Summary 1174.8 Acknowledgements 118References 1185 Redox-Responsive Disulphide Bioadhesive Polymeric Nanoparticles for Colon-Targeted Drug Delivery 123Erazuliana Abd Kadir and Vuanghao Lim5.1 Introduction 1235.2 Mechanism of Disulphide Bond Formation 1245.3 Disulphide Polymers for Colon Drug Delivery 1255.4 Colon-Targeted Drug Delivery (CTDD) 1265.4.1 Condition of the Colon for Drug Delivery 1275.4.2 Approaches for Colon Drug Delivery 1285.4.3 Limitations of CTDD 1295.5 Nanoformulations of Disulphide Polymers 1305.5.1 Thiolated Pectin Polymers 1305.5.2 Thiolated Sodium Alginate (TSA) Polymers 1315.5.3 Thiolated Chitosan (TCS) Polymers 1345.5.4 Thiolated Hyaluronic Acid Polymers 1365.5.5 Thiolated Dextran Polymers 1375.5.6 Other Thiolated Polymers 1385.6 Summary 140Acknowledgements 140References 1406 Bioadhesive Hydrogels and Their Applications 147Hitesh Chopra, Sandeep Kumar and Inderbir Singh6.1 Introduction 1476.1.1 Bioadhesive Polymer 1486.1.2 Hydrogels 1506.1.3 Bioadhesive Hydrogels 1556.2 Bioadhesive Hydrogel Films 1556.3 Bioadhesive Hydrogels for Gastrointestinal Delivery 1566.4 Bioadhesive Hydrogels Administered through Injection 1566.5 Bioadhesive Hydrogels for Vaginal Delivery 1596.6 Bioadhesive Hydrogels for Rectal Delivery 1606.7 Mucoadhesive Hydrogels Based Nanoparticles 1616.8 Patents and Future Perspectives 1616.9 Summary 164References 164Part 3: Drug Delivery Applications 1717 Ocular Bioadhesive Drug Delivery Systems and Their Applications 173Anju Sharma, Mukesh S. Patil, Pravin Pawar, A.A. Shirkhedkar and Inderbir Singh7.1 Introduction 1747.2 Anatomy and Physiology of the Eye 1757.2.1 Anatomy and Function of the Eye 1757.2.2 Structure of Cornea 1767.3 Various Bioadhesive/Mucoadhesive Polymers for Ocular Delivery 1767.3.1 Chitosan as Ocular Bioadhesive 1777.3.2 Starch (Drum-Dried Waxy Maize Starch, Pregelatinized Starch) 1807.3.3 Sodium Hyaluronate (SH) as Ocular Bioadhesive 1817.3.3.1 Functions of Sodium Hyaluronate 1817.3.3.2 Viscoelasticity 1827.3.3.3 Contact Angle 1827.3.3.4 Adherence to the Mucin Layer (Mucoadhesivity) 1837.3.3.5 Water Retention 1847.3.3.6 Healing of Superficial Keratitis 1847.3.3.7 Free Radical Scavenging 1847.3.4 Alginate Based Ocular Bioadhesive 1847.3.4.1 General Properties of ALGs 1857.3.5 Gellan Gum as Ocular Bioadhesive 1887.3.6 Albumin 1897.3.7 Collagen Based Ocular Bioadhesive 1907.3.8 Xanthan Gum 1927.3.9 Guar Gum 1937.3.10 Gelatin 1937.3.11 Tamarind Seed Polysaccharide (Xyloglucan) 1957.3.12 Arabinogalactan 1967.3.13 Gum Cordia 1977.3.14 Bletilla Striata Polysaccharide (BSP) 1977.3.15 Locust Bean Gum (Carob Bean Gum) 1987.3.16 Carrageenan 1987.4 Summary 199References 2008 Buccal Bioadhesive Drug Delivery Systems and Their Applications 213Veera Garg and Shammy Jindal8.1 Introduction 2138.1.1 Advantages of a Buccal Bioadhesive System 2188.1.2 Disadvantages of a Buccal Bioadhesive System 2188.1.3 Ideal Characteristics of a Bioadhesive Dosage Form 2198.1.4 Structure of Buccal Mucosa 2198.2 Theories of Bioadhesion 2208.2.1 Diffusion Theory 2218.2.2 Adsorption Theory 2228.2.3 Wetting Theory 2228.2.4 Electronic Theory 2228.2.5 Fracture Theory 2238.3 Factors Affecting Bioadhesion 2238.3.1 Bioadhesive Polymer Related Factors 2248.3.1.1 Molecular Weight of Mucoadhesive Polymer 2248.3.1.2 Cross-Linking of Mucoadhesive Polymer 2248.3.1.3 Concentration of Mucoadhesive Polymer 2248.3.1.4 Mucoadhesive Polymer Chain Length 2248.3.1.5 Flexibility of Mucoadhesive Polymer Chain 2258.3.1.6 Charge on Mucoadhesive Polymer 2258.3.1.7 H-Bonding of Mucoadhesive Polymer 2258.3.1.8 Spatial Configuration of Mucoadhesive Polymer 2258.3.1.9 Swelling of Mucoadhesive Polymer 2258.3.2 Environment Related Factors 2268.3.2.1 pH 2268.3.2.2 Saliva 2268.3.2.3 Salivary Gland 2268.3.2.4 Hydration 2268.3.2.5 Mucin Turnover 2278.3.2.6 Rate of Renewal of Mucoadhesive Cells 2278.3.2.7 Disease State 2278.3.2.8 Buccal Membrane Properties 2278.4 Mechanism of Buccal Absorption 2278.5 Buccal Bioadhesive Drug Delivery Systems 2298.5.1 Solid Buccal Bioadhesive Dosage Forms 2298.5.1.1 Buccal Tablets 2298.5.1.2 Microspheres 2308.5.1.3 Lozenges 2308.5.1.4 Wafers 2308.5.1.5 Gels 2308.5.1.6 Patches 2308.5.2 Liquid Dosage Forms 2318.6 Quality Control Tests of Buccal Bioadhesive Dosage Forms 2318.6.1 Moisture Absorption Test 2318.6.2 Swelling and Erosion Tests 2328.6.3 Tensile Strength and Elongation at Break 2328.6.4 Surface pH 2338.6.5 In-Vitro Bioadhesive Strength Measurement Test 2338.6.6 Residence Time 2348.6.6.1 Ex-Vivo Residence Time 2348.6.6.2 In-Vivo Residence Time 2348.6.6.3 Permeation Test 2348.6.6.4 Absorption Test 2368.7 Marketed Formulations 2368.8 Summary 236References 2379 Gastrointestinal Bioadhesive Drug Delivery Systems nd Their Applications 245Olufunke D. Akin-Ajani and Oluwatoyin A. OdekuAbbreviations 2459.1 Introduction 2469.2 The Mucus Layer 2479.3 Gastrointestinal Bioadhesive Drug Delivery Systems 2479.3.1 Solid Bioadhesive Formulations 2489.3.1.1 Tablets 2489.3.1.2 Bioadhesive Microparticles/Nanoparticles 2499.3.1.3 Bioadhesive Patches 2519.3.2 Semisolid Bioadhesive Formulations 2549.3.3 Liquid Bioadhesive Formulations 2549.3.3.1 Suspensions 2549.3.3.2 Bioadhesive Liquids 2559.4 Summary 255References 25510 Nasal Bioadhesive Drug Delivery Systems and Their Applications 259Ravindra V. Badhe and Sonali S. Nipate10.1 Introduction 26010.1.1 Nasal Route of Administration 26010.1.2 Nasal Cavity 26110.1.3 Nasal Route for Brain Drug Delivery 26310.1.4 Nasal Route for Local and Systemic Drug Delivery 26310.2 Challenges in Nasal Drug Delivery Formulations 26710.2.1 Ideal Properties of a Nasal Drug Delivery Formulation 26710.2.2 Strategies Developed for Improving Nasal Drug Delivery 26810.3 Mucoadhesion 27010.3.1 Physiology of Nasal Mucus Layer and Barriers Posed by It 27010.3.2 Factors Affecting Mucoadhesion 27110.3.3 Mucoadhesive Polymers Used in Nasal Delivery Formulations 27510.3.3.1 Chitosan and Its Composites 27510.3.3.2 Cellulose Derivatives 27710.3.3.3 Poloxamer or Pluronic 28410.3.3.4 Polyacrylates 28510.3.3.5 Lectin - Poly(ethylene glycol)(PEG) - Poly(lactic acid)(PLA)/Poly(lacticco-glycolic acid)(PLGA) 28610.3.3.6 Miscellaneous Mucoadhesive Agents 28710.4 Summary 289References 29011 Vaginal Bioadhesive Drug Delivery Systems and Their Applications 307Sanjeevani S. Deshkar, Satish V. Shirolkar and Arun T. Patil11.1 Introduction 30811.1.1 Advantages of Vaginal Drug Delivery 30811.1.2 Limitations 30911.2 Vaginal Anatomy and Physiology 30911.2.1 Vaginal Anatomy 30911.2.2 Physiology of Vagina 31011.2.2.1 Epithelium 31011.2.2.2 Vaginal Fluid 31111.2.2.3 pH 31111.2.2.4 Microflora 31211.2.2.5 Cyclic Changes 31211.2.2.6 Enzymes 31211.3 Vaginal Absorption of Drug 31311.3.1 Drugs Administered by Vaginal Route 31311.4 Conventional Drug Delivery Systems for Vaginal Application 31411.4.1 Vaginal Rings 31411.4.2 Vaginal Tablets 31511.4.3 Suppositories and Pessaries 31511.4.4 Semisolid Formulations 31611.4.5 Limitations of Conventional Vaginal Formulations 31611.5 Mucoadhesive Drug Delivery Systems 31711.5.1 Mucoadhesive Polymeric Platforms for Vaginal Drug Delivery 31811.5.1.1 Poly (acrylic acid) (PAA) Derivatives 31811.5.1.2 Cellulose Derivatives 31911.5.1.3 Natural Polymers 32111.5.1.4 New Generation Mucoadhesive Polymers 32411.5.2 Mucaodhesive Polymers as Enzyme Inhibitors and Permeation Enhancers 32511.5.3 Novel Mucoadhesive Formulations for Drug Delivery to Vagina 32611.5.3.1 Mucoadhesive Gels 32611.5.3.2 In Situ Gelling Systems 32711.5.3.3 Emulgels 33711.5.3.4 Vaginal Films 33711.5.3.5 Microparticulate Drug Delivery Systems 33811.5.3.6 Nanoparticle Based Drug Delivery Systems 33811.6 Recent Advancements in Vaginal Drug Delivery Applications 35011.6.1 Vaginal Immunization 35011.6.2 Gene Therapy 35011.6.3 Mucus Penetrating Nanoparticles 35111.6.4 Personalized Medicine Using Additive Manufacturing Technology 35111.7 Summary 352References 35212 Pulmonary Bioadhesive Drug Delivery Systems and Their Applications 371Ridhima Wadhwa, Subhashini Bharathala, Taru Aggarwal, Nikita Sehgal, Nitesh Kumar, Gaurav Gupta, Dinesh Kumar Chellappan, Pawan Kumar Maurya, Terezinha De Jesus Andreoli Pinto, Trudi Collet, Harish Dureja, Philip M. Hansbro and Kamal Dua12.1 Introduction to Pulmonary Drug Delivery Systems 37212.1.1 Deposition of Inhaled Particles 37312.1.2 Absorption of Inhaled Particles 37412.1.3 Challenges of Pulmonary Drug Delivery 37512.2 Bioadhesives in Pulmonary Drug Delivery Systems 37612.3 Development of Pulmonary Bioadhesive Drug Delivery Systems 37812.3.1 Nanoparticles 37812.3.2 Microparticles 38112.3.3 Liposomes 38312.4 Progress and Clinical Challenges for Bioadhesive Drug Delivery with Future Prospects 38412.4.1 Technological Advancements 38412.5 Future Prospects and Summary 385References 386Index 391

Kashmiri Lal Mittal was employed by the IBM Corporation from 1972 through 1993. Currently, he is teaching and consulting worldwide in the broad areas of adhesion as well as surface cleaning. He has received numerous awards and honors including the title of doctor honoris causa from Maria Curie-Sklodowska University, Lublin, Poland. He is the editor of more than 130 books dealing with adhesion measurement, adhesion of polymeric coatings, polymer surfaces, adhesive joints, adhesion promoters, thin films, polyimides, surface modification, surface cleaning, and surfactants. Dr. Mittal is also the Founding Editor of the journal Reviews of Adhesion and Adhesives.Inderbir Singh Bakshi obtained his PhD from Punjabi University, Patiala, India and is now working as Professor of Pharmaceutics at the College of Pharmacy, Chitkara University, Patiala, India. He has 17 years' experience in both industry and academia and has published 75 research/review articles in national & international journals, 3 books, 10 book chapters and seven patents (applied).Jasjeet Kaur Narang is an Associate Professor in the Department of Pharmaceutics, Khalsa College of Pharmacy, Amritsar, India. She obtained her M. Pharm and PhD from Jamia Hamdard University, New Delhi in 2001 and 2007 respectively. She did her post-doctorate work at the University of Montreal, Canada. She has published about 90 research articles in both international and national journals, authored three books and contributed many book chapters.

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