Title Details

Vijay Kumar Thakur (Ph.D.) is a Staff Scientist in the School of Mechanical and Materials Engineering at Washington State University, U.S.A. He has published more than 100 research articles, patents and conference proceedings in the field of polymers and materials science and has published ten books and 25 book chapters on the advanced state-of-the-art of polymers/ materials science. He has extensive expertise in the synthesis of polymers (natural/ synthetic), nano materials, nanocomposites, biocomposites, graft copolymers, high performance capacitors and electrochromic materials.

Manju Kumari Thakur works in the Department of Chemistry, Himachal Pradesh University, Simla, India.

Preface xv

1 Smart Hydrogels: Therapeutic Advancements in Hydrogel Technology for Smart Drug Delivery Applications 1
Gabriel Goetten de Lima, Diwakar Kanwar, Derek Macken, Luke Geever, Declan M. Devine and Michael J.D. Nugent

1.1 Introduction 1

1.2 Types and Properties of Smart Polymer Hydrogels 4

1.2.1 Temperature-Responsive Hydrogels 4

1.2.2 pH-Sensitive Hydrogels 5

1.2.3 Glucose-Responsive Hydrogels 7

1.2.4 Electro-Signal Sensitive Hydrogels 8

1.2.5 Light-Sensitive Hydrogels 8

1.2.6 Multi-Responsive Smart Hydrogels 10

1.3 Applications of Smart Polymer Hydrogels 11

1.4 Conclusion 11

References 13

2 Molecularly Imprinted Polymers for Pharmaceutical Applications 17
Ambareesh Kumar Singh, Neha Gupta, Juhi Srivastava, Archana Kushwaha and Meenakshi Singh

2.1 Introduction 17

2.2 Fluoroquinolone Antibiotics 19

2.3 Sulfonamides 36

2.4 Miscellaneous 41

2.5 Conclusions and Future Prospects 48

2.6 Acronyms and Abbreviations 48

References 50

3 Polymeric Stabilizers for Drug Nanocrystals 67
Leena Peltonen, Annika Tuomela and Jouni Hirvonen

3.1 Introduction 67

3.2 Methods for Nanocrystallization 68

3.2.1 Bottom-Up Technologies 69

3.2.2 Top-Down Technologies 69

3.2.3 Combination Technologies 71

3.4 Polymers for Nanocrystal Stabilization 73

3.4.1 Polymers of Natural Origin 75

3.4.2 Synthetic Polymers 77

3.5 Effect of Stabilizing Polymers on Drug Biocompatibility, Bioactivity, Membrane Permeability and Drug Absorption 79

3.6 Conclusions and Future Perspective 82

References 82

4 Polymeric Matrices for the Controlled Release of Phosphonate Active Agents for Medicinal Applications 89
Konstantinos E. Papathanasiou and Konstantinos D. Demadis

4.1 Introduction 89

4.2 Polymers in Drug Delivery 91

4.2.1 Polyesters 92

4.2.1.1 Poly(lactic acid), Poly(glycolic acid), and Their Copolymers 92

4.2.1.2 Poly(ethylene glycol) Block Copolymers 93

4.2.1.3 Poly(ortho esters) 94

4.2.1.4 Poly(anhydrides) 96

4.2.1.5 Poly(anhydride−imides) 97

4.2.1.6 Poly(anhydrite esters) 98

4.2.2 Poly(amides) 99

4.2.3 Poly(iminocarbonates) 100

4.3 Release of Phosphonate-Based Drugs 100

4.4 Conclusions/Perspectives 114

References 115

5 Hydrogels for Pharmaceutical Applications 125
Veena Koul, Sirsendu Bhowmick and Th anusha A.V.

5.1 Introduction 125

5.2 What are Hydrogels? 126

5.3 Classification of Hydrogels 126

5.4 Preparation of Hydrogels 127

5.5 Characterization of Hydrogels 128

5.6 Application of Hydrogels 131

5.6.1 Wound Dressing 131

5.6.2 Implantable Drug Delivery Systems 133

5.6.3 Tissue Engineering Substitute 134

5.6.4 Injectable Hydrogels 136

5.7 Conclusion 137

Acknowledgement 138

References 138

6 Responsive Plasmid DNA Hydrogels: A New Approach for Biomedical Applications 145
Diana Costa, Artur J.M. Valente and Joao Queiroz

6.2 DNA-Based Hydrogels 147

6.3 Controlled and Sustained Release 150

6.3.1 Photodisruption of Plasmid DNA Networks 150

6.3.2 Release of Plasmid DNA 152

6.3.3 Release of Chemotherapeutic Drugs 154

6.3.4 In Vitro Studies 155

6.4 Combination of Chemo and Gene Therapies 156

6.5 Conclusions and Future Perspectives 158

References 159

7 Bioactive and Compatible Polysaccharides Hydrogels Structure and Properties for Pharmaceutical Applications 163
Teresa Cristina F. Silva, Andressa Antunes Prado de Franca and Lucian A. Lucia

7.1 Introduction 163

7.2 Materials and Methods 164

7.2.1 Isolation of Xylans 166

7.2.1.1 Preparing Hydrogel without A Priori

Grafting of Vinyl Group 166

7.2.1.2 Preparing Hydrogels for Grafting Polymerization 166

7.2.2 Hydrogel Synthesis and Characterization 166

7.2.2.1 Preparing Hydrogel without A Priori Grafting of Vinyl Group 166

7.2.2.2 Preparing Hydrogels for Grafting Polymerization 166

7.2.3 Doxorubicin Release from Xylan-Based Hydrogels 167

7.3 Results and Discussion 167

7.3.1 Hydrogel without A Priori Grafting of Vinyl Group 167

7.3.1.1 Reaction of PAA with Wood 167

7.3.1.2 Hydrogel Preparation and Characterization 168

7.3.2 Hydrogels for Grafting Polymerization 170

7.3.2.1 Morphology and Rheological Properties 172

7.3.2.2 Swelling Behavior 173

7.3.2.3 Drug Release 174

References 175

8 Molecularly Imprinted Polymers for Pharmaceutical Analysis 179
Piotr Luliński

8.1 Introduction 179

8.2 Overview of the Imprinting Process 180

8.3 Molecularly Imprinted Polymers for Separation Purposes 182

8.3.1 Bulk Imprinted Materials 182

8.3.2 Imprinted Monoliths 185

8.3.3 Imprinted Stir-Bar Sorptive Extraction 187

8.3.4 Molecularly Imprinted Microparticles and Nanostructures 188

8.3.5 Magnetic Imprinted Materials 192

8.3.6 Miscellaneous Imprinted Formats 194

8.4 Molecularly Imprinted Sensors for Drugs 195

8.5 Conclusion and Future Perspective 197

References 1979 Prolamine-Based Matrices for Biomedical Applications 203
Pradeep Kumar, Yahya E. Choonara and Viness Pillay

9.1 Introduction 203

9.2 Gliadin – Prolamine Isolated from Wheat Gluten 204

9.2.1 Gliadin Nanoparticles 205

9.2.1.1 Hydrophobicity of Gliadin 206

9.2.1.2 Solubility Parameter 207

9.2.2 Controlled Drug Release from Gliadin-Based Matrices 207

9.2.2.1 Salting-Out 207

9.2.2.2 Gliadin Films 208

9.2.2.3 Gliadin Foams 209

9.3 Zein - Prolamine Isolated from Corn Gluten Meal 209

9.3.1 Drug-Loaded Zein Particulates 210

9.3.1.1 Microsphere-Based Films and Tablets 210

9.3.1.2 Zein-Based Blends and Complexes 213

9.3.1.3 Zein-Based Nanoparticulate Systems 213

9.3.2 Biomedical Applications of Zein-Based Matrices 215

9.4 Soy Protein – Prolamine Isolated from Soybean 217

9.4.1 Soy Protein Derivatives 218

9.4.2 Soy-Based Polymer Blends 218

9.4.3 Soy-Based Crosslinked Matrices 219

9.4.4 Cold-Set Gelation of Soy Protein 221

9.5 Kafi rin – Prolamine Isolated from Sorghum 222

9.5.1 Microparticles 223

9.5.2 Compressed Matrices 224

9.6 Conclusion and Future Perspective 224

References 225

10 Hydrogels Based on Poly(2-oxazoline) S for Pharmaceutical Applications 230
Anna Zahoranova and Juraj Kronek

10.1 Hydrogels for Medical Applications 231

10.1.1 Controlled Drug Delivery and Release 232

10.1.1.1 Prolonged Effect of Drugs 232

10.1.1.2 Stimuli-Sensitive Drug Delivery 234

10.1.2 3D Cell Cultivation 236

10.1.2.1 Chemical Composition 237

10.1.2.2 Porosity and Pore Size 238

10.1.3 Tissue Engineering 238

10.1.4 Nonenzymatic Detachment of Cells 239

10.2 Poly(2-oxazoline)s in Pharmaceutical Applications 240

10.2.1 Biocompatibility of Poly(2-oxazoline)s 241

10.2.2 Biomedical Applications of Poly(2-oxazoline)s 244

10.3 Poly(2-oxazoline)-Based Hydrogels – Synthetic Strategies 245

10.3.1 Hydrogels Containing Segments of Poly(2-oxazoline)s 245

10.3.2 Crosslinked Poly(2-oxazoline)s 248

10.4 Applications of Poly(2-oxazoline)-Based Hydrogels 250

10.4.1 Controlled Delivery of Drugs 250

10.4.1.1 Hydrogels for DNA Binding 251

10.4.1.2 Hydrogels Modifi ed by Peptidic Sequences 252

10.5 Conclusions and Future Perspectives 252

Acknowledgement 253

References 254

11 Mixed Biocompatible Block Copolymer/Lipid Nanostructures as Drug Nanocarriers: Advantages and Pharmaceutical Perspectives 259
Natassa Pippa, Stergios Pispas and Costas Demetzos

11.1 Introduction 259

11.2 Drug Delivery Systems 261

11.2.1 Conventional Drug Delivery Systems 261

11.2.2 Mixed Drug Delivery Systems Employing Biocompatible Polymers 263

11.3 Mixed Biocompatible Block Copolymer/Lipid Drug Nanocarriers: The Concept through Examples 266

11.3.1 Preparation of Mixed Drug Nanocarriers 266

11.3.2 Physicochemical Characterization of Mixed Drug Nanocarriers 267

11.3.3 Th ermotropic Behavior of Mixed Drug Nanocarriers 270

11.3.4 Imaging of Mixed Drug Nanocarriers 274

11.3.5 In Vitro Drug Release from the Mixed Nanocarriers 274

11.4 Conclusion and Future Perspective 277

References 279

12 Nanoparticle Polymer-Based Engineered Nanoconstructs for Targeted Cancer Th erapeutics 287
Anand Thirunavukarasou, Sudhakar Baluchamy and Anil K. Suresh

12.1 An Overview of Metal Polymer-Based Nanoconstructs 287

12.1.1 Tumor-Specific Targeting Using Nanoparticle-Polymer Nanoconstructs 290

12.1.2 Cytotoxicity Assessments of Nanoparticle-Polymer Constructs 291

12.1.2.1 MTT and/or MTS Assay 291

12.1.2.2 Live/Dead Staining Assay 291

12.1.3 Physical Characterization Techniques to Assess the Cellular Uptake of the Nanoparticle-Polymer Constructs 292

12.1.3.1 Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) for Quantitative Uptake 292

12.1.3.2 Dark Field Microscopy 292

12.1.3.3 Ultramicrotome-Based Trans-Sectional Transmission Electron Microscopy Imaging 293

12.2 Conclusions 293

Acknowledgements 294

References 294

13 Th e Importance of Dendrimers in Pharmaceutical Applications 297

Veronica Brunetti, Marisa Martinelli and Miriam C. Strumia

13.1 Introduction 297

13.1.1 What are Dendrimers? 298

13.1.2 Synthetic Methods for Dendritic Molecules 300

13.1.2.1 Divergent Synthesis 300

13.1.2.2 Convergent Synthesis 301

13.2 Properties of Dendritic Polymers Useful for Biomedical Applications 301

13.3 Current Pharmaceutical Products Prepared from Dendritic Polymer:

Promising Prospects for Future Applications 303

13.3.1 Diagnostic Technologies 303

13.3.2 Dendritic Polymers in Prevention 304

13.3.3 Therapeutic Applications 307

13.4 Conclusions 310

References 310

14 Pharmaceutical Polymers: Bioactive and Synthetic Hybrid Polymers 315
Roxana Cristina Popescu and Alexandru Mihai Grumezescu

14.1 Introduction 315

14.2 General Obtainment Methods for Polymeric Microspheres and Hybrid Materials 320

14.3 Stimuli-Responsive (pH/temperature/photo) polymers 321

14.3.1 PEG 321

14.3.2 PLA and PLGA 325

14.3.3 PVP 328

14.3.4 PVA 333

14.4 Conclusions 333

Acknowledgements 334

References 334

15 Eco-friendly Polymer-Based Nanocomposites for Pharmaceutical Applications 341
Ida Idayu Muhamad, Suguna Selvakumaran, Mohd Harfi z Salehudin and Saiful Izwan Abd Razak

15.1 Introduction 342

15.1.1 Eco-friendly Polymers, the Briefs 342

15.1.2 Composite 342

15.1.3 Nanocomposites 343

15.1.4 Eco-friendly Nanocomposite 343

15.1.5 Market Trend in Eco-friendly Polymer Nanocomposites in Biomedical Application 344

15.2 Structure and Properties of Some Eco-friendly Pharmaceutical Polymers 345

15.2.1 Starch 346

15.2.2 Chitosan 347

15.2.2.1 Application of Chitosan 348

15.2.3 Alginate (E400-E404) 349

15.2.4 Polyhydroxyalkanoates (PHAs) 349

15.2.5 Poly(lactic acid) (PLA) 350

15.2.6 Gelatin 351

15.2.7 Casein Protein 351

15.2.8 Carrageenan 352

15.3 Review of Development and Application of Selected Eco-friendly Polymer-Based Nanocomposites 355

15.3.1 Eco-friendly Polymer Matrix Nanocomposites for Tissue Engineering 355

15.3.2 Polymer Nanocomposites in Drug Delivery 356

15.3.3 Nanocomposite-Based Biosensor on Eco-friendly Polymer 358

15.3.4 Polymer Nanocomposite-Based Microfluidics 359

15.4 Case Study on Carrageenan-Based Nanocomposite 360

15.4.1 Carrageenan-Based Metalic Nanocomposite 360

15.4.2 Advantageous of Metalic Nanocomposite in Pharmaceutical Applications 366

15.5 Summary 366

References 367

16 Biodegradable and Biocompatible Polymers-Based Drug Delivery Systems for Cancer Th erapy 373
Ibrahim M. El-Sherbiny, Nancy M. El-Baz and Amr H. Mohamed

16.1 Introduction 373

16.1.1 Cancer-Targeted Therapy 376

16.2 Selection Considerations of Polymers for Drug Delivery 377

16.2.1 Biodegradability 377

16.2.2 Biocompatibility 379

16.2.3 Surface Modification 379

16.3 Types of Biodegradable Polymers 381

16.3.1 Natural Biodegradable Polymers 381

16.3.1.1 Protein-Based Biodegradable Polymers 381

16.3.1.2 Polysaccharides-Based Biodegradable Polymers 382

16.3.2 Synthetic Biodegradable Polymers 384

16.3.2.1 Polyesters 384

16.4 Preparation Methods of Biodegradable Polymeric Carriers 387

16.4.1 Polymer Dispersion 388

16.4.1.1 Emulsion-Solvent Evaporation Method 388

16.4.1.2 Double Emulsion Method 389

16.4.1.3 Nanoprecipitation 389

16.4.1.4 Salting Out 389

16.4.2 Polymerization 389

16.4.2.1 Emulsion Polymerization 390

16.4.2.2 Microemulsion Polymerization 390

16.4.3 Ionic Gelation 390

16.4.4 Spray Drying 391

16.5 Recent Applications of Biodegradable Polymers-Based Targeted Drug Delivery for Cancer Therapy 391

16.5.1 Passive Cancer-Targeted Delivery 392

16.5.1.1 Stealth Liposomes and Nanoparticles 393

16.5.2 Active Cancer-Targeted Drug Delivery Systems 395

16.5.3 Stimuli-Responsive Polymeric Drug Delivery 396

16.6 Conclusion 400

References 400

Index 407