Mucoadhesive Materials and Drug Delivery Systems

<p>List of Contributors xv</p>
<p>Preface xvii</p>
<p>Section One Structure and Physiology of Mucosal Surfaces in Relation to Drug Delivery 1</p>
<p>1 Oral Mucosa: Physiological and Physicochemical Aspects 3<br /> Gleb E. Yakubov, Hannah Gibbins, Gordon B. Proctor and Guy H. Carpenter</p>
<p>1.1 Anatomical and Histological Aspects of Oral Cavity Tissues 3</p>
<p>1.2 Production and Composition of Saliva 8</p>
<p>1.3 Surface Architecture, Mechanical, Rheological and Transport Properties of Salivary Pellicle 16</p>
<p>1.4 Future Perspective 27</p>
<p>References 27</p>
<p>2 Anatomy of the Eye and the Role of Ocular Mucosa in Drug Delivery 39<br /> Peter W.J. Morrison and Vitaliy V. Khutoryanskiy</p>
<p>2.1 Introduction 39</p>
<p>2.2 Anatomy of the Eye 40</p>
<p>2.3 Introduction to Ocular Mucosa 45</p>
<p>2.4 The Role of Ocular Mucosa in Drug Delivery 47</p>
<p>2.5 Models for Ocular Drug Delivery 48</p>
<p>2.6 Recent Advances in Topical Ocular Drug Delivery 51</p>
<p>2.7 Conclusions 55</p>
<p>References 55</p>
<p>3 Drug Delivery Across the Nasal Mucosa 61<br /> Michelle Armstrong, Shonagh Walker, Jenifer Mains and Clive G. Wilson</p>
<p>3.1 Introduction 61</p>
<p>3.2 Drug Delivery via the Nasal Mucosa 63</p>
<p>3.3 Anatomy and Physiology of the Nasal Cavity 66</p>
<p>3.4 Disease States of the Nasal Cavity 70</p>
<p>3.5 Transport Across the Membrane 73</p>
<p>3.6 Nose–to–Brain Drug Delivery 75</p>
<p>3.7 Conclusion 76</p>
<p>References 76</p>
<p>4 Gastrointestinal Mucosa and Mucus 83<br /> Felipe O. Varum and Abdul W. Basit</p>
<p>4.1 Introduction 83</p>
<p>4.2 The Gastrointestinal Mucus 86</p>
<p>4.3 Conclusions 94</p>
<p>References 94</p>
<p>5 Vaginal Mucosa and Drug Delivery 99<br /> Jos&eacute; das Neves, Rita Palmeira–de–Oliveira, Ana Palmeira–de–Oliveira, Francisca Rodrigues and Bruno Sarmento</p>
<p>5.1 Introduction 99</p>
<p>5.2 Drug Delivery and the Human Vagina 100</p>
<p>5.3 Vaginal Drug Dosage Forms 105</p>
<p>5.4 Novel Strategies for Enhanced Vaginal Drug Delivery 110</p>
<p>5.5 Mucoadhesion and the Vaginal Environment 111</p>
<p>5.6 Vaginal Microbicides 114</p>
<p>5.7 Users Acceptability and Preferences 116</p>
<p>5.8 Conclusions and Future Perspectives 118</p>
<p>Acknowledgements 118</p>
<p>References 119</p>
<p>Section Two Understanding of Mucoadhesion and Methods of Investigation 133</p>
<p>6 Structure and Properties of Mucins 135<br /> Monica Berry and Anthony Corfield</p>
<p>6.1 Introduction 135</p>
<p>6.2 General Characteristics of Mucins 136</p>
<p>6.3 Mucin Glycosylation Changes in Disease 139</p>
<p>6.4 Dynamics of Mucin Synthesis and Function 142</p>
<p>6.5 Mucin Gel Formation on Cell Surfaces 143</p>
<p>6.6 Mucin Therapeutics 148</p>
<p>6.7 Polysaccharide Coatings to Enable Probiotic Delivery 149</p>
<p>6.8 Gene Cloning and Drug Delivery 149</p>
<p>6.9 Chemo–Enzymatic Synthesis of O–Glycans for Drug Delivery 149</p>
<p>6.10 Glycan Legislation 150</p>
<p>References 151</p>
<p>7 Theories of Mucoadhesion 159<br /> John D. Smart</p>
<p>7.1 Introduction 159</p>
<p>7.2 Mucous Membranes 159</p>
<p>7.3 Mucoadhesives 160</p>
<p>7.4 The Adhesive Interaction 160</p>
<p>7.5 Mucoadhesion 162</p>
<p>7.6 Solid Mucoadhesion 162</p>
<p>7.7 Semi–solid Mucoadhesion 168</p>
<p>7.8 Liquid Mucoadhesion 169</p>
<p>7.9 Modified Materials 169</p>
<p>7.10 Conclusions 170</p>
<p>References 170</p>
<p>8 Methods to Study Mucoadhesive Dosage Forms 175<br /> Maya Davidovich–Pinhas and Havazelet Bianco–Peled</p>
<p>8.1 Introduction 175</p>
<p>8.2 Model Surfaces for Mucoadhesion Evaluation 176</p>
<p>8.3 Methods to Evaluate Mucoadhesion Dosage Form 177</p>
<p>8.4 Summary 189</p>
<p>References 189</p>
<p>9 Methods for Assessing Mucoadhesion: The Experience of an Integrative Approach 197<br /> Gleb E. Yakubov, Scott Singleton and Ann–Marie Williamson</p>
<p>9.1 Mucins and Mucosal Architecture 197</p>
<p>9.2 Concept of Length and Time Scales in Mucoadhesion 198</p>
<p>9.3 Experimental Approaches to Measuring Mucosal Interactions 201</p>
<p>9.4 Integrative Approaches. Layer–by–Layer Assembled Multilayers: A Tool for Studying Mucoadhesion 208</p>
<p>9.5 Future Perspective 224</p>
<p>References 225</p>
<p>Section Three Mucoadhesive Materials 233</p>
<p>10 Chitosan 235<br /> Joshua Boateng, Isaac Ayensu and Harshavardhan Pawar</p>
<p>10.1 Introduction 235</p>
<p>10.2 Material and Physicochemical Properties of Chitosan 236</p>
<p>10.3 Applications 240</p>
<p>10.4 Material Characterisation of Bioadhesive Chitosan Formulations 245</p>
<p>10.5 Summary 247</p>
<p>References 247</p>
<p>11 Thiomers 255<br /> Christiane M&uuml;ller and Andreas Bernkop–Schn&uuml;rch</p>
<p>11.1 Introduction 255</p>
<p>11.2 Thiolated Polymers 257</p>
<p>11.3 Sulfhydryl Group Contribution 260</p>
<p>11.4 Mechanism of Mucoadhesion 262</p>
<p>11.5 Mucoadhesive Properties 263</p>
<p>11.6 Additional Properties of Thiolated Polymers 264</p>
<p>11.7 Mucoadhesive Dosage Forms Based on Thiomers 267</p>
<p>11.8 Biopharmaceutical Use of Thiomers 269</p>
<p>11.9 Safety and Stability 272</p>
<p>11.10 Conclusion 273</p>
<p>References 273</p>
<p>12 Boronate–Containing Polymers 279<br /> Alexander E. Ivanov</p>
<p>12.1 Introduction 279</p>
<p>12.2 Fundamentals of Borate and Boronate Interactions with Monoand Oligosaccharides 280</p>
<p>12.3 Multipoint Association of BCPs with Polysaccharides 282</p>
<p>12.4 Formation of Interpolymer Complexes of BCPs with Mucin Glycoprotein 284</p>
<p>12.5 Interaction of BCPs with Animal Cells 286</p>
<p>12.6 Polymeric Mucoadhesive Materials and Devices Employing Boronate Carbohydrate Interactions 289</p>
<p>12.7 Conclusions 291</p>
<p>References 292</p>
<p>13 Liposome–Based Mucoadhesive Formulations 297<br /> Kohei Tahara and Hirofumi Takeuchi</p>
<p>13.1 Introduction 297</p>
<p>13.2 Oral Administration of Surface–Modified Liposomes with the Mucoadhesive Properties 298</p>
<p>13.3 The Behaviour of Liposomes After Oral Administration 300</p>
<p>13.4 Pulmonary Administration of Peptide Drugs with Liposomal Formulations: Effective Surface Modification Using Chitosan or Poly(Vinyl Alcohol) with a Hydrophobic Anchor 301</p>
<p>13.5 Modification of Liposomes Using Mucoadhesive Polymer Wheat Germ Agglutinin Conjugates for Pulmonary Drug Delivery 304</p>
<p>13.6 Conclusions 306</p>
<p>References 306</p>
<p>14 Acrylated Polymers 309<br /> Maya Davidovich–Pinhas and Havazelet Bianco–Peled</p>
<p>14.1 Introduction 309</p>
<p>14.2 Mucoadhesion 310</p>
<p>14.3 Types of Interactions Involved in the Mucoadhesion Process 310</p>
<p>14.4 Interactions Between Acrylate and Mucin Glycoprotein 311</p>
<p>14.5 Acrylated Alginate (Alginate–PEGAc) 314</p>
<p>14.6 Summary 325</p>
<p>References 325</p>
<p>Index 329</p>