كتاب Advanced Healthcare Materials

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Advanced Healthcare Materials
من سلسلة علم المواد المتقدمة
Advanced Material Series
Ashutosh Tiwari
Biosensors and Bioelectronics Centre, Link?ping University, Sweden

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Contents
Preface xvii
List of Contributors xix
Part 1: Functional Terapeutics 1
1 Stimuli-Responsive Smart Nanoparticles for Biomedical Application 3
Arnab De, Sushil Mishra and Subho Mozumdar
1.1 A Brief Overview of Nanotechnology 4
1.2 Nanoparticulate Delivery Systems 5
1.3 Delivery Systems 6
1.3.1 Hydrogels 6
1.3.2 Dendrimers 7
1.3.3 Liposomes 8
1.3.4 Niosomes 8
1.3.5 Polymersomes 9
1.3.6 Solid Lipid Nanoparticle (SLN) 10
1.3.7 Micro- and Nanoemulsions 11
1.3.8 Micelles 12
1.3.9 Carbon Nanomaterials 13
1.4 Polymers for Nanoparticle Synthesis 13
1.4.1 Polyesters 13
1.4.2 Poly-?-caprolactone 14
1.4.3 Poly(alkyl cyanoacrylates) 15
1.4.4 Polyethylene Glycol 16
1.5 Synthesis of Nanovehicles 17
1.5.1 Top-Down Approach 17
1.5.2 Bottom-Up Approach 18
1.5.3 Hybrid Approach 18
1.6 Dispersion of Preformed Polymers 18
1.6.1 Emulsifcation-Solvent Evaporation 18
1.6.2 Solvent-Displacement, -Di?usion, or
Nanoprecipitation 19vi Contents
1.6.3 Emulsifcation-Solvent Di?usion (ESD) 20
1.6.4 Salting-Out 20
1.6.5 Dialysis 21
1.6.6 Supercritical Fluid Technology 21
1.7 Emulsion Polymerization 22
1.7.1 Conventional Emulsion Polymerization 22
1.7.2 Surfactant-Free Emulsion Polymerization 22
1.7.3 Mini-Emulsion Polymerization 23
1.7.4 Micro-Emulsion Polymerization 23
1.7.5 Interfacial Polymerization 23
1.8 Purifcation of Nanoparticle 24
1.8.1 Evaporation 24
1.8.2 Filtrations Trough Mesh or Filters 24
1.8.3 Centrifugation 25
1.8.4 Ultracentrifugation 25
1.8.5 Dialysis 25
1.8.6 Gel Filtration 26
1.9 Drying of Nanoparticles 26
1.9.1 Freeze Drying 26
1.9.2 Spray-Drying 27
1.10 Drug Loading 27
1.11 Drug Release 28
1.12 Conclusion 29
References 29
2 Diagnosis and Treatment of Cancer—Where We are and
Where We have to Go! 37
Rajiv Lochan Gaur and Richa Srivastava
2.1 Cancer Pathology 38
2.2 Cancer Diagnosis 39
2.3 Treatment 43
Conclusion 44
References 44
3 Advanced Materials for Biomedical Application and
Drug Delivery 49
Salam J.J. Titinchi, Mayank P. Singh, Hanna S. Abbo
and Ivan R. Green
3.1 Introduction 50
3.2 Anticancer Drug Entrapped Zeolite Structures as Drug
Delivery Systems 50Contents vii
3.3 Mesoporous Silica Nanoparticles and Multifunctional
Magnetic Nanoparticles in Biomedical Applications 54
3.4 BioMOFs: Metal-Organic Frameworks for Biological and
Medical Applications 66
3.4.1 Introduction 66
3.4.2 Synthesis, Properties and Structures of MOFs 67
3.4.3 MOFs as Drug Delivery Agents 69
3.4.4 Applications of MOFs as NO storage 73
3.4.5 Applications of Bio-MOFs as Sensors 75
3.5 Conclusions 77
References 77
4 Nanoparticles for Diagnosis and/or Treatment of
Alzheimer’s Disease 87
S.G. Antimisiaris, S. Mourtas, E. Markoutsa, A. Skouras,
and K. Papadia
4.1 Introduction 87
4.2 Nanoparticles 88
4.2.1 Types of NPs Used for Terapy and/or Diagnosis 91
4.2.2 Physicochemical Properties and their E?ect
on the in vivo Fate of Nanoparticle Formulations 96
4.3 Physiological Factors Related with Brain-Located
Pathologies: Focus on AD 98
4.3.1 Neurodegenerative Diseases; AD and Related
Pathologies 98
4.3.2 Te Blood Brain Barrier (BBB) 99
4.3.2.1 BBB Physiology 99
4.3.2.2 Methods to Overcome the BBB 102
4.3.3 In vitro and in vivo Models for BBB Permeability and
AD Diagnostic/Terapeutic Approach Assesment 106
4.3.3.1 In vitro Methods 106
4.3.3.2 In vivo (and in situ) Methods 108
4.4 Current Methodologies to Target AD-Related Pathologies 112
4.4.1 Tau-targeted Strategies—Available Ligands 112
4.4.1.1 Ligands Available for Tau Targeting 119
4.4.2 Amyloid Plaque or A?- species Targeted Strategies 123
4.4.2.1 A? Peptide Formation 123
4.4.2.2 A? Transport Across the BBB-Strategies
for Terapy 124
4.4.2.3 A? Peptide Species 125
4.4.2.4 Ligands Available to Target A? 126viii Contents
4.4.3 Is Passing the BBB Always Needed?—Sink Teory 135
4.4.4 Functionalization of Ligands to NPs 135
4.5 Nanoparticles for Diagnosis of AD 138
4.5.1 Introduction 138
4.5.2 Organic NPs for AD Diagnosis 138
4.5.3 Inorganic NPs for AD Diagnosis 144
4.5.4 Other NP-Types for Diagnosis of AD 147
4.6 Nanoparticles for Terapy of AD 148
4.6.1 Polymeric NPs for Terapy of AD 148
4.6.2 Lipidic NPs for T erapy of AD 156
4.6.3 Other NP Types 158
4.7 Summary of Current Progress and Future Challenges 162
Acknowledgments 163
References 163
Part 2: Point-of-care Diagnostics 181
5 Novel Biomaterials for Human Health: Hemocompatible
Polymeric Micro- and Nanoparticles and Teir Application
in Biosensor 183
Chong Sun, Xiaobo Wang, Chun Mao and Jian Shen
5.1 Introduction 183
5.2 Design and Preparation of Hemocompatible Polymeric
Micro- and Nanoparticles 185
5.3 Te Biosafety and Hemocompatibility Evaluation System
for Polymeric Micro- and Nanoparticles 187
5.3.1 In vitro Coagulation Time Tests 188
5.3.2 Complement and Platelet Activation Detection 188
5.3.3 Percent Hemolysis of RBCs 190
5.3.4 Morphological Changes of RBCs 190
5.3.5 Cytotoxic Assessment 191
5.4 Construction of Biosensor for Direct Detection
in Whole Blood 192
5.4.1 Evaluation of GOx/(Hep-PU) Hybrids 192
5.4.2 Evaluation of Whole Blood Adhesion Tests 193
5.4.3 Direct Electrochemistry of GOx/(Hep-PU)/
GCE and Calibration Curve 195
5.4.4 Human Blood Samples Measurement 197
5.5 Conclusion and Prospect 198
References 199Contents ix
6 Te Contribution of Smart Materials and Advanced Clinical
Diagnostic Micro-Devices on the Progress and Improvement
of Human Health Care 203
F.R.R. Teles and L.P. Fonseca
6.1 Introduction 204
6.2 Physiological Biomarkers as Targets in Clinical
Diagnostic Bioassays 206
6.2.1 Small Analytes 206
6.2.2 Antigens and Antibodies 206
6.2.3 Nucleic Acids 207
6.2.4 Whole Cells 208
6.3 Biosensors 209
6.3.1 Principles and Transduction Mechanisms 209
6.3.2 Immunosensors vs. Genosensors 211
6.3.3 Optical vs. Electrochemical Detection 212
6.3.4 Merging Electrochemistry with Enzyme Biosensors 214
6.3.5 Strip-Tests and Dipstick Tests 215
6.3.6 Biosensor Arrays and Multiplexing 216
6.3.7 Micro?uidic-Based Biosensors 217
6.3.8 Lab-on-a-chip (LOC) 220
6.4 Advanced Materials and Nanostructures for Health
Care Applications 221
6.5 Applications of Micro-Devices to Some Important
Clinical Pathologies 227
6.5.1 Diabetes 227
6.5.2 Cholesterol and Cardiovascular Disease 229
6.5.3 Cancer 230
6.6 Conclusions and Future Prospects 231
Acknowledgment 231
References 232
Part 3: Translational Materials 237
7 Hierarchical Modeling of Elastic Behavior of Human Dental
Tissue Based on Synchrotron Di?raction Characterization 239
Tan Sui and Alexander M. Korsunsky
7.1 Introduction 239
7.2 Experimental Techniques 242
7.2.1 Micro-CT Protocol 242
7.2.2 In situ X-Ray Scattering Measurements 242x Contents
7.2.2.1 Mechanical Loading Setup 242
7.2.2.2 Beamline Di?raction Setup 244
7.3 Model Formulation 244
7.3.1 Geometrical Assumptions 244
7.3.1.1 Dentine Hierarchical Structure 244
7.3.1.2 Enamel Hierarchical Structure 246
7.3.2 Multi-Scale Eshelby Model 247
7.3.2.1 First-Level Eshelby Model 247
7.3.2.2 Second-Level Eshelby Model 248
7.4 Experimental Results and Model Validation 251
7.4.1 Nano-Scale HAp Distribution and Mechanical
Response 251
7.4.2 Evaluation and Testing of the Multi-Scale
Eshelby Model 256
7.5 Discussion 257
7.5.1 Refned Parameters of the Two-Level Eshelby Model 257
7.5.2 Residual Strain 258
7.5.3 Normal Strain Components Variation 258
7.5.4 HAp Crystals Distribution E?ects 259
7.6 Conclusions 261
Acknowledgments 262
Appendix 262
References 266
8 Biodegradable Porous Hydrogels 269
Martin Pradny, Miroslav Vetrik, Martin Hruby and Jiri Michalek
8.1 Introduction 269
8.2 Methods of Preparation of Porous Hydrogels 271
8.2.1 Crosslinking Polymerization in the Presence of
Substances that are Solvents for Monomers, but
Precipitants for the Formed Polymer 271
8.2.2 Crosslinking Polymerization in the Presence
of Solid Porogen 272
8.2.3 Crosslinking Polymerization in the Presence of
Substances Releasing a Gas 273
8.2.4 Freeze-Drying (Lyophilization) of the Hydrogel
Swollen in Water 274
8.2.5 Fibrous Materials 274
8.2.6 Cryogelation 275
8.2.7 Combined Techniques 276Contents xi
8.3 Hydrogels Crosslinked With Degradable Crosslinkers 277
8.3.1 Hydrogels Degradable by Hydrolysis of the
N-O Bonds 278
8.3.2 Hydrolytic Splitting of Crossing Chain Based on
Poly(Caprolactone) 279
8.3.3 Reductive Splitting of S-S Bond which is Part of
Crossing Chain 280
8.4 Hydrogels Degradable in the Main Chain 282
8.4.1 Polycaprolactone-Based Hydrogels 282
8.4.2 Polysacharide-Based Hydrogels 283
8.4.3 Polylactide-Based Hydrogels 284
8.4.4 Polyvinylalcohol-Based Hydrogels 285
8.4.5 Poly(ethylene oxide)-Based Hydrogels 286
8.4.6 Peptide-Based Hydrogels 286
8.5 Conclusions 287
Acknowledgments 287
References 289
9 Hydrogels: Properties, Preparation, Characterization and
Biomedical Applications in Tissue Engineering, Drug
Delivery and Wound Care 295
Mohammad Sirousazar, Mehrdad Forough, Khalil Farhadi,
Yasaman Shaabani and Rahim Molaei
9.1 Introduction 295
9.2 Types of Hydrogels 296
9.3 Properties of Hydrogels 301
9.4 Preparation Methods of Hydrogels 305
9.4.1 Physical Methods 305
9.4.1.1 Crosslinking by Ionic Interactions 305
9.4.1.2 Crosslinking by Hydrogen Bonds 306
9.4.1.3 Crosslinking by Heating/Cooling 306
9.4.1.4 Crosslinking by Crystallization 307
9.4.1.5 Crosslinking by Maturation 308
9.4.2 Chemical Methods 309
9.4.2.1 Crosslinking of Polymer Chains 309
9.4.2.2 Grafing 310
9.4.2.3 Crosslinking Using Enzymes 311
9.5 Characterization of Hydrogels 311
9.5.1 Infrared Spectroscopy 311
9.5.2 X-Ray Di?raction Analysis (XRD) 312
9.5.3 Nuclear Magnetic Resonance (NMR) 312xii Contents
9.5.4 Atomic Force Microscopy (AFM) 312
9.5.5 Di?erential Scanning Calorimetry (DSC) 313
9.5.6 Electron Microscopy 313
9.5.7 Chromatography 314
9.5.8 Other Techniques 314
9.6 Biomedical Applications of Hydrogels 314
9.6.1 Tissue Engineering 317
9.6.2 Drug Delivery 319
9.7 Hydrogels for Wound Management 325
9.7.1 Wound Care and Wound Dressings 325
9.7.2 Types of Wound Dressings 327
9.7.3 Hydrogel Wound Dressings 331
9.7.3.1 Preparation Methods of Hydrogel
Wound Dressings 335
9.7.3.2 Characterization of Hydrogel Wound
Dressings 339
9.8 Recent Developments on Hydrogels 343
9.9 Conclusions 346
References 347
Part 4: Emerging Bio-engineering Devices 359
10 Modifed Natural Zeolites—Functional Characterization
and Biomedical Application 361
Jela Mili?, Aleksandra Dakovi?, Danina Kraji?nik
and George E. Rottinghaus
10.1 Introduction 362
10.1.1 Clinoptilolite 363
10.1.2 Biomedical Application of Natural Zeolites 366
10.2 Surfactant Modifed Zeolites (SMZs) 367
10.2.1 Application of SMZs as Sorbents of Mycotoxins 369
10.3 Minerals as Pharmaceutical Excipients 374
10.3.1 Minerals and Modifed Drug Delivery 376
10.3.2 Clinoptilolite as Potential Pharmaceutical
Excipient/Drug Delivery 376
10.4 SMZs for Pharmaceutical Application 380
10.4.1 Preparation and Characterization of SMZs
for Drug Delivery 380
10.4.1.1 Physicochemical Analysis of ZCPCs 384
10.4.1.2 Evaluation of Possible SMZs
Pharmaceutical Application 391Contents xiii
10.5 Conclusions 397
Acknowledgement 398
References 398
11 Supramolecular Hydrogels Based on Cyclodextrin
Poly(Pseudo)Rotaxane for New and Emerging Biomedical
Applications 405
Jin Huang, Jing Hao, Debbie P. Anderson and Peter R. Chang
11.1 Introduction 406
11.2 Fabrication of Cyclodextrin Poly(pseudo)rotaxane-Based
Hydrogels 408
11.2.1 Homopolymers as Guest Molecules 408
11.2.2 Block-Copolymers as Guest Molecules 412
11.2.2.1 Diblock Copolymer 412
11.2.2.2 Triblock Copolymer 413
11.2.3 Graf-Copolymers as Guests 414
11.2.4 Other Branched Polymers as Guests 415
11.3 Stimulus-Response Properties of Cyclodextrin
Poly(pseudo)rotaxane Based Hydrogels 417
11.3.1 Stimulus-Response Properties Derived from
Cyclodextrin Poly(pseudo)rotaxanes and their
Aggregates 418
11.3.1.1 Shear-Tinning 418
11.3.1.2 Temperature-sensitivity 419
11.3.2 Stimulus-Response Properties Derived from
Uncovered Segments 420
11.3.2.1 pH Sensitivity 420
11.3.2.2 Reduction Sensitivity 421
11.4 Nanocomposite Supramolecular Hydrogels 421
11.4.1 Nanocomposite Hydrogel Filled with Carbon
Nanoparticles 422
11.4.2 Nanocomposite Hydrogels Filled with
Metal-Based Nanoparticles 423
11.4.3 Nanocomposite Hydrogel Filled with
Polysaccharide Nanoparticles 425
11.4.4 Role of Nanoparticles 425
11.4.4.1 Reinforcement 426
11.4.4.2 Other Functions 428
11.5 Biomedical Application of Cyclodextrin
Poly(pseudo)rotaxane-Based Hydrogels 428xiv Contents
11.5.1 Drug Carriers 428
11.5.2 Gene Carriers 431
11.5.3 Cell-Adhesive Sca?old 432
11.6 Conclusions and Prospects 433
References 433
12 Polyhydroxyalkanoate-Based Biomaterials for Applications
in Biomedical Engineering 439
Chenghao Zhu and Qizhi Chen
12.1 Introduction 440
12.2 Synthesis of PHAs 441
12.3 Processing and its In?uence on the Mechanical
Properties of PHAs 443
12.4 Mechanical Properties of PHA Sheets/Films 444
12.5 PHA-Based Polymer Blends 447
12.5.1 Miscibility of PHAs with Other Polymers 447
12.5.2 Degradability of PHA-Based Polymer Blends 451
12.5.3 Biocompatibility of PHA-Based Polymer Blends 453
12.5.4 Mechanical Properties of PHA-Based
Polymer Blends 454
12.6 Summary 459
References 459
13 Biomimetic Molecularly Imprinted Polymers as Smart
Materials and Future Perspective in Health Care 465
Mohammad Reza Ganjali, Farnoush Faridbod
and Parviz Norouzi
13.1 Molecularly Imprinted Polymer Technology 466
13.2 Synthesis of MIPs 466
13.2.1 Molecular Covalent Imprinting Polymer 469
13.2.2 Molecular Non-Covalent Imprinting Polymer 470
13.2.3 Nano-Molecularly Imprinted Polymers
(Nano-MIPs) 470
13.3 Application of MIPs 471
13.4 Biomimetic Molecules 472
13.5 MIPs as Receptors in Bio-Molecular Recognition 473
13.6 MIPs as Sensing Elements in Sensors/Biosensors 474
13.7 MIPs as Drug Delivery Systems 475
13.8 MIPs as Sorbent Materials in Separation Science 483Contents xv
13.9 Future Perspective of MIP Technologies 488
13.10 Conclusion 488
References 488
14 Te Role of Immunoassays in Urine Drug Screening 493
Niina J. Ronkainen and Stanley L. Okon
14.1 Introduction 494
14.2 Urine and Other Biological Specimens 497
14.3 Immunoassays 499
14.3.1 Assay Design 501
14.3.2 Antibody–Antigen Interactions 502
14.3.3 Common Immunoassay Formats for
Drug Screening 505
14.3.3.1 Enzyme Immunoassays 505
14.3.4 Fluorescent Immunoassays 509
14.3.4.1 Fluorescence Polarization
Immunoassay (FPIA) 509
14.3.5 Immunoturbidimetric Assay 510
14.3.5.1 Kinetic Interaction of Microparticles
in Solution Immunoassays (KIMS) 511
14.3.6 Lateral Flow Immunoassay 512
14.4 Drug Screening with Immunoassays 512
14.4.1 On-Site Drug Testing 512
14.4.2 Point of Care Drug Testing 513
14.5 Immunoassay Specifcity: False Negative and False
Positive Test Results 515
14.6 Confrmatory Secondary Testing Using Chromatography
Instruments 518
14.6.1 Gas Chromatography–Mass
Spectrometry (GC-MS) 519
14.6.2 Liquid chromatography–Mass Spectrometry/
Mass Spectrometry (LC-MS/MS) 520
Conclusion 521
References 522
Index 52

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