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Bücher | Nanotechnologie | Nanomaterialien | Nanomaterials for Medical Diagnosis and Therapy | Inhaltsverzeichnis
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  Contents  
 
  Foreword VII
  Preface XXI
  List of Contributors XXVII
1 Nanotechnologies for Diagnosis -- Present and Future
Gareth A. Hughes 		1
1.1 Introduction to Patient Diagnostics 1
1.2 Nanotechnology and Patient Diagnostics 2
1.3 Optical 9
1.3.1 Fluorescence 9
1.3.2 Quantum Dots 11
1.3.3 Surface Plasmon Resonance (SPR), Nanoparticles and Nanoshells 14
1.3.4 Fiber Optic Biosensors 19
1.4 Electrical 19
1.4.1 Nanomaterials for Enhanced Electron Transfer 20
1.4.2 Electrochemical Biosensors 24
1.5 Magnetic 28
1.6 Mechanical 30
1.7 Imaging Diagnostics 33
1.8 Nanotechnology-enhanced Tools 34
1.8.1 Analytical Tools 35
1.8.2 Raman Spectroscopy 35
1.8.3 Mass Spectrometry 36
1.8.4 Genetics 37
1.8.5 Immunoassays 39
1.9 Nanotechnology and the Future of Patient Diagnostics 40
1.9.1 Multifunctional Platforms 40
1.9.2 Real-time Monitoring 40
1.9.3 Multiplexed Diagnostic Assays 40
1.9.4 Point-of-care Diagnostics 41
1.9.5 Regulations, Risks and Ethics 42
References 44
2 Superparamagnetic Nanoparticles of Iron Oxides for Magnetic Resonance Imaging Applications
Jean-Marc Idee, Marc Port, Isabelle Raynal, Michel Schaefer, Bruno Bonnemain, Philippe Prigent, Philippe Robert, Caroline Robic, and Claire Corot 		51
2.1 Introduction 51
2.2 Physicochemical Characteristics 53
2.2.1 Physicochemical Properties of the Crystal 54
2.2.2 Hydrodynamic Particle Size and Charge 54
2.3 Pharmacology and Metabolism 56
2.3.1 Role of Physicochemical Parameters 57
2.3.2 Mechanism and Consequences of Interaction with Macrophages 58
2.3.3 Pharmacokinetics 59
2.3.4 Nanoparticle Vectorization 60
2.4 Current Clinical Uses and Future Developments 61
2.4.1 Gastrointestinal Tract Imaging 61
2.4.2 Liver and Spleen Diseases 63
2.4.3 Lymph Node Metastases 64
2.4.4 Blood Pool Characteristics 66
2.4.5 Characterization of the Atheromatous Plaque 67
2.4.6 Other Potential Uses 68
2.4.6.1 Stroke 68
2.4.6.2 Cerebral Tumor Characterization 68
2.4.6.3 Multiple Sclerosis 69
2.4.6.4 Arthritis 70
2.4.6.5 Infection 70
2.4.6.6 Kidney Imaging 71
2.4.6.7 Acute Cardiac Transplant Rejection 72
2.4.6.8 In Vivo Monitoring of Cell Therapy 72
2.4.6.9 T-staging of Uterine Neoplasms 73
2.4.6.10 MRI-detectable Embolotherapy 73
2.5 Conclusion 75
References 76
3 Carbon Nanotube-based Vectors for Delivering Immunotherapeutics and Drugs
Alberto Bianco, Wei Wu, Giorgia Pastorin, Cédric Klumpp, Lara Lacerda, Charalambos D. Partidos, Kostas Kostarelos, and Maurizio Prato 		85
3.1 Introduction 85
3.2 Chemical Functionalization of CNTs 86
3.2.1 Noncovalent Functionalization 86
3.2.1.1 - Stacking Interactions 86
3.2.1.2 Hydrophobic Interactions 88
3.2.2 Covalent Functionalization 89
3.2.2.1 Defect Functionalization 90
3.2.2.2 Sidewall Functionalization 91
3.3 CNTs in Diagnosis 96
3.3.1 CNTs in FETs 97
3.3.1.1 Fabrication 97
3.3.1.2 FET Biosensors 98
3.3.2 CNT-based Electrodes 100
3.3.2.1 Fabrication 101
3.3.2.2 Nanoelectrode Biosensors 102
3.4 CNT Cell Uptake 105
3.5 CNTs as Delivery Devices for Antigens and Adjuvants 107
3.5.1 Interaction of -CNTs with CpG Motifs and Potentiation of their Immunostimulatory Activity 107
3.5.2 Presentation and Immunogenic Potential of Peptide Antigens Attached onto -CNTs 109
3.6 CNTs for Drug Delivery 111
3.7 CNTs for Gene Transfer 115
3.7.1 Interaction with DNA and RNA 115
3.7.2 Delivery and Expression of Gene-encoding DNA and RNA 116
3.8 Health Impact of CNTs 118
3.8.1 Parameters of CNTs Related to Health Impact 119
3.8.1.1 Purity 119
3.8.1.2 Solvents 123
3.8.1.3 Surface of CNTs 123
3.8.1.4 Length 123
3.8.2 In Vitro Effect of CNTs 123
3.8.3 In Vivo Effects of CNTs 125
3.9 General Conclusions 127
Acknowledgments 128
References 128
4 Core--Shell Nanoparticles for Drug Delivery and Molecular Imaging
Sung Kyun Han, Ree Sun Kim, Jin Ho Lee, Giyoong Tae, Sun Hang Cho, and Soon Hong Yuk 		143
4.1 Introduction 143
4.2 Core--shell Nanoparticles with a Lipid Core 145
4.3 Core--Shell Nanoparticles with a Polymeric Core 156
4.3.1 Hyaluronic Acid (HA)-functionalized PLGA Nanoparticles 157
4.3.2 Heparin-functionalized PLGA Nanoparticles 166
4.4 Core--shell Nanoparticles with a Metallic Core 174
4.5 Conclusions 181
Acknowledgments 181
References 182
5 Nanotechnologies for Targeted Delivery of Drugs
Pavel Bro and Patrick Hunziker 		189
5.1 Introduction 189
5.2 Basic and Special Pharmacology 192
5.2.1 Outline 192
5.2.2 Basic Pharmacology 193
5.2.2.1 Absorption 193
5.2.2.2 Bioavailability 196
5.2.2.3 Distribution 197
5.2.2.4 Elimination 198
5.2.3 Special Pharmacology 201
5.2.3.1 Skin Epithelium 201
5.2.3.2 Mucosal Epithelium of the Respiratory Tract 202
5.2.3.3 Mucosal Epithelium of the Gastrointestinal Tract 202
5.2.3.4 Mononuclear Phagocyte System (MPS) 204
5.2.3.5 Endothelial Barrier 206
5.2.3.6 Cell Membrane 207
5.3 Strategies for Targeted Delivery -- Observed in Nature 209
5.3.1 Outline 209
5.3.2 Bacteria 210
5.3.2.1 Host Invasion 210
5.3.2.2 Immune System Evasion 213
5.3.3 Viruses 215
5.3.3.1 Immune System Evasion 216
5.3.3.2 Host Cell Invasion 217
5.3.3.3 Viral Vectors for Therapeutic Applications 219
5.3.4 Prions 221
5.4 Strategies for Targeted Delivery -- Designed by Man 223
5.4.1 Outline 223
5.4.2 Noninvasive Delivery Systems 223
5.4.2.1 Oral Delivery Systems 224
5.4.2.2 Transdermal Delivery Systems 224
5.4.2.3 Transmucosal Delivery Systems 225
5.4.3 Invasive Delivery Systems 225
5.4.4 Targeted Delivery to the Brain 226
5.4.5 Macrophage Targeting 228
5.4.6 Other Targets 230
5.5 Conclusion and Outlook 233
References 234
6 Nanoporous and Nanosize Materials for Drug Delivery Systems
Yoshinobu Fukumori, Kanji Takada and Hirofumi Takeuchi 		255
6.1 Introduction 255
6.2 Nanomaterials for Coating 256
6.2.1 Commercially Available Aqueous Polymeric Nanomaterials 257
6.2.2 Novel Terpolymer Nanoparticles for Coating 259
6.2.3 Core--shell Nanoparticles for Fine Particle Coating 260
6.2.4 Core--Shell Nanoparticles for Thermosensitively Drug-releasing Microcapsules 261
6.2.5 Chitosan Nanoparticles for Microparticle Coating 263
6.3 Materials for Nanoparticulate Therapy and Diagnosis 264
6.3.1 Inorganic Nanoparticles 265
6.3.2 Polymeric Nanoparticles 267
6.3.3 Other Case Studies 267
6.4 Nanoporous Materials as Drug Delivery System Carriers 270
6.4.1 Inorganic Calcium Compounds 270
6.4.2 Silastic Compounds 271
6.4.2.1 Nanoporous Silastic Materials for Solidifying Oily Drugs 271
6.4.2.2 Nanoporous Silastic Materials for Poorly Absorbable Drugs 275
6.4.2.3 Nanoporous Silica Materials for Controlled Release of Drugs 278
6.4.3 Carbon Nanotubes (CNTs) 280
6.4.3.1 CNTs for Oral Delivery of Protein Drug 280
6.4.3.2 CNTs for Intracellular Delivery of Protein 282
6.4.3.3 Toxicity of CNTs 284
6.4.3.4 Functionalized CNTs (-CNTs) for Drug Delivery 285
6.4.3.5 -CNTs for Gene Delivery 286
6.4.4 CNHs for Drug Delivery 286
6.5 Physicochemical Aspects of Porous Silastic Materials for Drug Delivery 287
6.5.1 Solid Dispersion Particles with Porous Silica 288
6.5.2 Mesoporous Silica 295
References 299
7 NANOEGG(R) Technology for Drug Delivery
Yoko Yamaguchi and Rie Igarashi 		310
7.1 Introduction 310
7.2 New Nanoparticles with a Core--Shell Structure: The NANOEGG System 311
7.2.1 Physicochemical Properties and Action of ATRA 311
7.2.2 NANOEGG Preparation and Characterization 314
7.2.3 Improved Lability of ATRA in the NANOEGG System 317
7.3 NANOEGG for Dermatological Aspects 319
7.3.1 Improved Irritation of ATRA in the NANOEGG System 320
7.3.2 Pharmacological Effects of the NANOEGG System 323
7.3.3 Expression of mRNA Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) on Mouse Skin 325
7.3.4 Proliferation and Differentiation of Keratinocytes 326
7.3.5 Production of Hyaluronic Acid (HA) in the Epidermal Layer 328
7.3.6 Hyperpigmentation and Fine Wrinkle Improvements by NANOEGG Treatment on Animal Skin 330
7.3.7 Clinical Trials of Fine Wrinkles and Brown Spots on the Human Face 331
7.4 Why does NANOEGG Show the High Performance on the Improvement of Brown Spot and Wrinkles? 334
7.5 NANOEGG for Other Indications 335
7.6 NANOEGG for Other Drugs 338
7.7 Conclusion 338
References 339
8 Polymeric Nanomaterials -- Synthesis, Functionalization and Applications in Diagnosis and Therapy
Jutta Rieger, Christine Jérôme, Robert Jérôme, and Rachel Auzély-Velty 		342
8.1 Introduction 342
8.2 Polymer Materials Used for the Synthesis of Nanoparticles 345
8.2.1 Natural Polymers 346
8.2.2 Degradable Synthetic Polymers 349
8.2.3 Nondegradable Synthetic Polymers 352
8.2.4 PEO 352
8.3 Preparation of Polymeric Nanoparticles 354
8.3.1 Preparation of Nanospheres from Preformed Polymers 354
8.3.1.1 Emulsion-evaporation 354
8.3.1.2 Salting-out 355
8.3.1.3 Emulsification-diffusion 356
8.3.1.4 Nanoprecipitation 356
8.3.2 Synthesis of Nanospheres by In Situ Polymerization 357
8.3.3 Preparation of Nanocapsules 358
8.4 Surface Functionalization 359
8.4.1 Functionalization with Biological (Macro)molecules 359
8.4.2 Functionalization with Specific Ligands: Specific Interaction through Biological Recognition 360
8.4.2.1 Mono- or Oligosaccharides (Carbohydrates) 360
8.4.2.2 Folate Receptor 361
8.4.2.3 Antibodies 362
8.4.2.4 Biotin 362
8.4.3 Strategies for Surface Modification 363
8.4.3.1 Adsorption on Preformed Nanoparticles 364
8.4.3.2 Functional Surfactants as Stabilizers and Surface Modifiers 366
8.4.3.3 Emulsion, Miniemulsion or Dispersion Polymerization 369
8.4.3.4 Covalent Linking of Functional Molecules to Preformed Nanoparticles 370
8.4.4 Analytical Techniques for Surface Modification 375
8.4.4.1 Physicochemical Techniques 376
8.4.4.2 Biological Assays/Methods 377
8.5 Applications 380
8.5.1 Drug Delivery Systems 380
8.5.1.1 Routes of Administration 380
8.5.1.2 Therapeutic Applications of Nanoparticles 382
8.5.1.3 Triggered Release 384
8.5.2 Diagnosis 388
8.5.2.1 Fluorescence Labeling of Polymeric Nanoparticles 388
8.5.2.2 Contrast Agents for MRI 392
8.5.2.3 Magnetic Nanoparticles for In Vitro Assays 393
8.5.2.4 Electron Dense Agents for Transmission Electron Microscopy (TEM) 396
8.5.2.5 Radiolabeled Nanoparticles 396
8.6 Conclusion and Perspectives 396
References 397
9 Polymeric Nanoparticles for Drug Delivery
Paraskevi Kallinteri and Martin C. Garnett 		409
9.1 Introduction: Application of Nanoparticles for Noncancer Applications 409
9.1.1 Physiological and Uptake of Particles 410
9.1.1.1 Routes of Tissue and Cellular Uptake of Particles 410
9.1.1.2 Uptake by Macrophages and Lymphoid Tissues 411
9.1.1.3 Mucosal-associated Lymphoid Tissues (MALT) 411
9.1.2 Routes of Delivery 412
9.1.2.1 Oral 412
9.1.2.2 Nasal 413
9.1.2.3 Pulmonary 413
9.1.2.4 Transdermal/Subcutaneous 414
9.2 Drug Delivery 415
9.2.1 Ocular Delivery 415
9.2.1.1 Anatomy of the Eye 415
9.2.1.2 Pathology 416
9.2.1.3 Drug Delivery 416
9.2.1.4 Tolerability 422
9.2.1.5 Future Prospects for Nanoparticles in Ocular Delivery 422
9.2.2 Macrophage-related Diseases 423
9.2.2.1 Leishmaniasis 423
9.2.2.2 Other Parasitic Infections 426
9.2.3 Antifungal 427
9.2.3.1 Treatment 427
9.2.3.2 Drug Delivery Systems 428
9.2.4 Tuberculosis 431
9.2.4.1 Physiology and Pathology 431
9.2.4.2 Treatment 431
9.2.4.3 Future Prospects 434
9.2.5 AIDS 434
9.2.5.1 Pathology 434
9.2.5.2 Treatment 434
9.2.5.3 Nanoparticle Delivery Systems 435
9.2.5.4 Vaccines and AIDS 439
9.2.6 Vaccines 441
9.2.6.1 Delivery Route 442
9.2.7 Diabetes 451
9.2.7.1 Treatment 451
9.2.7.2 Delivery Routes 452
9.3 Conclusions 460
References 461
10 Solid Lipid and Polymeric Nanoparticles for Drug Delivery
José Luis Pedraz, Gorka Orive, Manoli Igartua, Alicia R. Gascón, Rosa M. Hernández, Maria Angeles Solinis, and Amaia Esquisabel 		471
10.1 Introduction 471
10.2 SLNs 472
10.2.1 Introduction 472
10.2.2 Composition 473
10.2.3 Production Processes 474
10.2.3.1 Preparation Techniques 474
10.2.3.2 Scaling-up, Sterilization and Drying 475
10.2.4 Drug Incorporation, Loading, Incorporation Efficiency, Nanoparticle Recovery and Drug Release 476
10.2.4.1 Drug Incorporation 476
10.2.4.2 Drug Loading 477
10.2.4.3 Determination of Nanoparticle Recovery and Drug Incorporation Efficiency 477
10.2.4.4 Drug Release 478
10.2.5 Related Structures and Stability 478
10.2.6 Analytical Characterization of SLNs 480
10.2.6.1 Particle Size 480
10.2.6.2 The Potential 481
10.2.6.3 Crystallinity and Polymorphism and Colloidal Structures 481
10.2.7 Applications 481
10.2.7.1 Gene Therapy 482
10.2.7.2 Peptide and Protein Delivery 486
10.2.7.3 Low-soluble Drugs 488
10.2.7.4 Topical and Transdermal Administration 490
10.2.7.5 Cosmetic Applications for SLNs 491
10.3 Polymeric Nanoparticles 491
10.3.1 Introduction 491
10.3.2 Nanoparticle Preparation Methods 492
10.3.2.1 Nanoparticles Prepared by In Situ Polymerization of Monomers 492
10.3.2.2 Nanoparticles Prepared from Preformed Polymers 493
10.3.3 Characterization of Polymeric Nanoparticles 494
10.3.4 Pharmaceutical Applications of Nanoparticles 495
10.3.4.1 Protein Delivery 495
10.3.4.2 Protein Delivery by Mucosal Routes 496
10.3.4.3 Vaccine Adjuvants 498
References 499
11 Intelligent Hydrogels in Nanoscale Sensing and Drug Delivery Applications
J. Zach Hilt 		509
11.1 Introduction 509
11.2 Intelligent Hydrogels 510
11.2.1 Ionic Hydrogels 510
11.2.2 Temperature-responsive Hydrogels 510
11.2.3 Biohybrid Hydrogels 510
11.2.4 Imprinted Hydrogels 511
11.3 Sensor Applications 511
11.3.1 Actuation Detection 511
11.3.2 Optical Detection 513
11.3.3 Electrical Detection 517
11.4 Drug Delivery Applications 519
11.4.1 Micro/nanoscale Devices 520
11.4.2 Nanoscale Macromolecular Structures 520
11.5 Conclusions 522
References 522
12 Nanoshells for Drug Delivery
Melgardt M. De Villiers and Yuri Lvov 		527
12.1 Introduction 527
12.2 Metallic Nanoshells 528
12.2.1 Synthesis of the Nanoshells 528
12.2.2 Application in Nanomedicine 530
12.3 Nanoshells Formed by Polyion E-LbL Self-assembly 532
12.3.1 Preparation of E-LbL Nanoshells 532
12.3.1.1 Proving the Nanoshells 535
12.3.1.2 Influence of the Core on Nanoshell Properties 538
12.3.1.3 Barrier Properties of E-LbL Assembled Nanoshells 539
12.3.2 Controlled Release of Active Pharmaceutical Ingredients Encapsulated by E-LbL Assembled Nanoshells 540
12.3.2.1 Nanoshell Permeability for Low-molecular-weight Compounds 542
12.3.2.2 Nanoshell Permeability for High-molecular-weight Compounds 543
12.3.3 E-LbL Assembled Nanoshells as Protective and Functional Barriers 545
12.3.4 Magnetic Nanoshells 548
12.3.5 Nano-organized Shells with Functions other than a Adjustable Diffusion Barrier 550
12.3.5.1 Colloidal Stabilization 550
12.3.5.2 Interpolyelectrolyte Complex Formation 550
12.3.5.3 Biomimetic Approach 551
12.4 Conclusion 552
References 553
13 Bionanoparticles and their Biomedical Applications
L. Andrew Lee, Hannah N. Barnhill, and Qian Wang 		557
13.1 Introduction 557
13.2 BNPs 558
13.3 Genetic and Chemical Alterations of BNPs 560
13.3.1 Chemical Modifications 560
13.3.1.1 Conventional Bioconjugation Methods for Selective Modifications 560
13.3.1.2 ``Click Chemistry'' for Bioconjugation of BNPs 567
13.3.1.3 New Developments in Tyrosine Modification 569
13.3.2 Genetic Alterations 570
13.3.2.1 Heterologous Peptide Insertions 571
13.3.2.2 NAA Substitutions 576
13.3.2.3 Protein Expression Systems 576
13.4 BNPs in Therapeutics 577
13.4.1 Cell Targeting 578
13.4.2 Gene Delivery 579
13.4.3 Bioimaging 580
13.4.4 Drug Encapsulation and Release 583
13.5 Immune Response 584
13.5.1 Vaccine Development 584
13.5.2 Immune Modulation 585
13.6 Future Directions 586
Acknowledgments 587
References 587
14 Nanotechnology for Gene Therapy -- HVJ-E Vector
Hironori Nakagami, Yasuhiko Tabata, and Yasufumi Kaneda 		597
14.1 Introduction 597
14.2 Biological Barriers to Gene Transfer 599
14.2.1 Reaching Target Cells 599
14.2.1.1 Recognition by Specific Target Tissues 599
14.2.1.2 Avoidance of Nonspecific Uptake 599
14.2.1.3 Resistance to Degradation in Systemic Circulation 600
14.2.2 Crossing the Cell Membrane 600
14.2.3 Nuclear Targeting 601
14.2.4 Regulation of Gene Expression 602
14.2.4.1 Stable Retention of Transgenes 602
14.2.4.2 Regulation of Transcription 603
14.3 HVJ-E Vector 604
14.3.1 Development of HVJ-E Vector 604
14.3.2 Approaches to Cancer Gene Therapy Utilizing HVJ-E Vector 609
14.3.2.1 Transfection of Dendritic Cells (DCs) with Melanoma-associated Antigen (MAA) using HVJ Envelope Vector for Immunotherapy of Melanoma 609
14.3.2.2 Fusion of DC Tumor Cells and Simultaneous Gene Transfer to the Hybrid Cells using HVJ-E for the Prevention and Treatment of Cancers 611
14.4 Biocompatible Polymer with HVJ-E 613
14.5 Magnetic Nanoparticles for Medicine 615
14.6 Conclusion 620
References 620
15 Nanotoxicology of Synthetic Gene Transfer Vectors: Poly(ethyleneimine)- and Polyfectin-mediated Membrane Damage and Apoptosis in Human Cell Lines
Seyed M. Moghimi 		629
15.1 Introduction 629
15.2 PEI as a Nonviral Vector 630
15.2.1 Structure and Properties of PEI and PEI--DNA Complexes 630
15.2.2 Cytotoxicity 630
15.3 PEI-mediated Cell Dysfunction and Apoptosis 631
15.3.1 PEI and PEI--DNA Complex Internalization 631
15.3.2 Plasma Membrane Damage and Apoptosis 632
15.3.3 Effect of PEI on the Function of Isolated Mitochondria 634
15.3.4 Other Plausible Apoptotic Routes 637
15.4 Cell Damage and Apoptosis with Related Polycations and Cationic Lipids 638
15.5 Conclusions and Future Outlook 639
References 640
16 Nanoparticles for the Treatment of Alzheimer's Disease: Theoretical Rationale, Present Status and Future Perspectives
Gang Liu, Ping Men, George Perry and Mark A. Smith 		644
16.1 Introduction 644
16.2 Rationales: The Ability of Nanoparticles to Cross the BBB -- A Useful Tool to Deliver Drugs into the Brain 645
16.2.1 Physiological Functions of the BBB 645
16.2.2 Strategies for Drug BBB Penetration 646
16.2.3 Preparation of Polymeric Nanoparticulate Drug Delivery Systems 648
16.2.4 Possible Mechanisms by which Nanoparticles Cross the BBB 650
16.3 Status: Nanoparticle Targeting Transport of Therapeutic Agents for Potential Treatment of AD 652
16.3.1 Nanoparticle Targeting of A to Deliver Potentially Therapeutic Agents 652
16.3.2 Nanoparticulate Antioxidant Delivery to Increase Efficacy against A-mediated Oxidative Stress 653
16.3.3 Nanoparticle Delivery of Copper Chelator for Preventing and Reversing A Deposition 657
16.3.4 Nanoparticle Transport of Iron Chelators and Metal Chelator Complexes Into and Out of the Brain, Respectively 661
16.3.4.1 Increased Levels of Various Metals in the Brain of AD Patients 661
16.3.4.2 Problems with Iron Chelators for Simultaneous Removal of Multimetal Ions for Treatment of AD 662
16.3.4.3 Nanoparticle Transport Technology to Improve Chelation Therapy for AD 665
16.3.4.4 Experimental Descriptions 666
16.3.4.5 Results and Discussion 676
16.4 Perspectives 683
Acknowledgments 685
References 685
  Index 707

 
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