Preface xv
Part I: Biomedical nanomaterials
1 Nanoemulsions: Preparation, Stability and Application in Biosciences 1
Thomas Delmas, Nicolas Atrux-Tallau, Mathieu Goutayer, SangHoon Han, Jin Woong Kim, and Jérôme Bibette
1.1 Introduction 2
1.2 Nanoemulsion:A Thermodynamic De¿nition and Its Practical Implications 5
1.2.1 Generalities on Emulsions 5
1.2.2 Nanoemulsion vs. Microemulsion, a Thermodynamic De¿nition 6
1.3 Stable Nanoemulsion Formulation 9
1.3.1 Nanoemulsion Production 9
1.3.2 Nanoemulsion Stability Rules 11
1.3.3 Nanoemulsion Formulation Domain 16
1.3.4 Conclusion on the Formulation of Stable Nanoemulsions 21
1.4 Nanoencapsulation in Lipid Nanoparticles 21
1.4.1 Aim ofActive Encapsulation 21
1.4.2 Lipid Complexity and In¿uence of Their Physical State 23
1.4.3 Amorphous Lipids for a Large Range of Encapsulated Molecules 27
1.4.4 Lipids Viscosity and Release 31
1.4.5 Conclusion on the Use ofAmorphous Lipid Matrices for Control OverActive Encapsulation and Release 34
1.5 Interactions between Nanoemulsions and the Biological Medium: Applications in Biosciences 35
1.5.1 Nanoemulsion Biocompatibility 35
1.5.2 Classical TargetingApproach by Chemical Grafting - Example of Tumor Cell Targeting by Crgd Peptide for Cancer Diagnosis and Therapy 38
1.5.3 New 'No Synthesis Chemistry'Approach - Example of Pal-KTTKS andAsiaticoside Targeting for CosmeticActives Delivery 41
1.5.4 Conclusion on Nanoemulsions Application in Biosciences 46
1.6 General Conclusion 47
References 48
2 Multifunctional Polymeric Nanostructures for Therapy and Diagnosis 57
Angel Contreras-García and Emilio Bucio
2.1 Introduction 58
2.2 Polymeric-based Core-shell Colloid 61
2.3 Proteins and Peptides 64
2.4 Drug Conjugates and Complexes with Synthetic Polymers 65
2.5 Dendrimers, Vesicles, and Micelles 67
2.5.1 Dendrimers 67
2.5.2 Vesicles 68
2.5.3 Micelles 70
2.6 Smart Nanopolymers 71
2.6.1 Temperature and pH Stimuli-responsive Nanopolymers 72
2.6.2 Hydrogels 72
2.6.3 Stimuli Responsive Biomaterials 73
2.6.4 Interpenetrating Polymer Networks 74
2.7 Stimuli Responsive Polymer-metal Nanocomposites 75
2.8 Enzyme-responsive Nanoparticles 78
Acknowledgements 83
References 83
3 Carbon Nanotubes: Nanotoxicity Testing and Bioapplications 97
R. Sharma and S. Kwon
3.1 Introduction 98
3.1.1 What is Nanotoxicity of Nanomaterials? 98
3.2 Historical Review of Carbon Nanotube 99
3.3 Carbon Nanotubes (CNTs) and Other Carbon Nanomaterials 100
3.3.1 Physical Principles of Carbon Nanotube Surface Science 102
3.4 Motivation - Combining Nanotechnology and Surface Science with Growing Bioapplications 104
3.5 Cytotoxicity Measurement and Mechanisms of CNT Toxicity 111
3.1.6 In Vivo Studies on CNT Toxicity 113
3.1.7 In¿ammatory Mechanism of CNT Cytoxicity 114
3.1.8 Characterization and Toxicity of SWCNT and MWCNT Carbon Nanotubes 116
3.6 MSCs Differentiation and Proliferation on Different Types of Scaffolds 120
3.6.1 An In Vivo Model CNT-Induced In¿ammatory Response in Alveolar Co-culture System 122
3.6.2 Static Model: 3-Dimensional Tissue Engineered Lung 124
3.6.3 Dynamic Model: Integration of 3D Engineered Tissues into Cyclic Mechanical Strain Device 126
3.6.4 In Vivo MR Microimaging Technique of Rat Skin Exposed to CNT 127
3.7 New Lessons on CNT Nanocomposites 130
3.8 Conclusions 135
Part II: Advanced nanomedicine
4 Discrete Metalla-Assemblies as Drug Delivery Vectors 149
Bruno Therrien
4.1 Introduction 149
4.2 Complex-in-a-Complex Systems 150
4.3 Encapsulation of Pyrenyl-functionalized Derivatives 155
4.4 Exploiting the Enhanced Permeability and Retention Effect 159
4.5 Incorporation of Photosensitizers in Metalla-assemblies 162
4.6 Conclusion 165
Acknowledgments 165
References 166
5 Nanomaterials for Management of Lung Disorders and Drug Delivery 169
Jyothi U. Menon, Aniket S. Wadajkar, Zhiwe iXie, and Kytai T. Nguyen
5.1 Lung Structure and Physiology 170
5.2 Common Lung DiseasesAnd Treatment Methods 171
5.2.1 Lung Cancer 171
5.2.2 PulmonaryArterial Hypertension 172
5.2.3 Obstructive Lung Diseases 173
5.3 Types of Nanoparticles (NPs) 173
5.3.1 Liposomes 174
5.3.2 Micelles 176
5.3.3 Dendrimers 177
5.3.4 Polymeric Micro/Nanoparticles 177
5.4 Methods for Pulmonary Delivery 179
5.4.1 Nebulization 179
5.4.2 Metered Dose Inhalation (MDI) 182
5.4.3 Dry Powder Inhalation (DPI) 183
5.4.4 IntratrachealAdministration 183
5.5 Targeting Mechanisms 184
5.5.1 Passive Targeting 184
5.5.2 Active Targeting 185
5.5.3 Cellular Uptake Mechanisms 188
5.6 TherapeuticAgents Used for Delivery 188
5.6.1 ChemotherapeuticAgents 188
5.6.2 Bioactive Molecules 190
5.6.3 Combinational Therapy 190
5.7 Applications 191
5.7.1 Imaging/DiagnosticApplications 191
5.7.2 TherapeuticApplications 193
5.7.3 Lung Remodeling and Regeneration 194
5.8 Design Considerations of NPs 195
5.8.1 Half-life of NPs 195
5.8.2 Drug Release Mechanisms 195
5.8.3 Clearance Mechanisms in the Lung 196
5.9 Current Challenges and Future Outlook 197
6 Nano-Sized Calcium Phosphate (CaP) Carriers for Non-Viral Gene/Drug Delivery 199
Donghyun Lee, Geunseon Ahn and Prashant N. Kumta
6.1 Introduction 200
6.2 Vectors for Gene Delivery 202
6.2.1 Viral Vectors 203
6.2.2 Non-viral Vectors 203
6.2.3 Calcium Phosphate Vectors 205
6.3 Modulation of Protection and Release Characteristics of Calcium Phosphate Vector 213
6.4 Calcium Phosphate Carriers for Drug Delivery Systems 219
6.4.1 Antibiotics Delivery 219
6.4.2 Growth Factor Delivery 221
6.5 Variants of Nano-calcium Phosphates: Future Trends of the CaPDelivery Systems 221
Acknowledgements 223
References 223
7 Organics Modi¿edMesoporous Silica for Controlled Drug Delivery Systems 233
Jingke Fu, Yang Zhao, Yingchun Zhu and Fang Chen
7.1 Introduction 233
7.2 Controlled Drug Delivery Systems Based on Organics Modi¿ed
7.2.1 MSNs-based Drug Delivery Systems Controlled by Physical Stimuli 238
7.2.2 MSNs-based Drug Delivery Systems Controlled by Chemical Stimuli 246
7.3 Conclusions 258
References 259
Part III: Nanotheragnostics
8 Responsive Polymer-Inorganic Hybrid Nanogels for Optical Sensing, Imaging, and Drug Delivery 263
Weitai Wu and Shuiqin Zhou
8.1 Introduction 264
8.2 Mechanisms of Response 268
8.2.1 Reception of an External Signal 268
8.2.2 Volume Phase Transition of the Hybrid Nanogels 275
8.2.4 Regulated Drug Delivery 282
8.3 Synthesis of Responsive Polymer-inorganic Hybrid Nanogels 285
8.3.1 Synthesis of the Hybrid Nanogels from Pre-synthesized Polymer Nanogels 285
8.3.2 Synthesis of the Hybrid Nanogels from Pre-synthesized Inorganic NPs 289
8.3.3 Synthesis of the Hybrid Nanogels by a Heterogeneous Polymerization Method 292
8.4 Applications 293
8.4.1 Responsive Polymer-inorganic Hybrid Nanogels in Optical Sensing 293
8.4.2 Responsive Polymer-inorganic Hybrid Nanogels in Diagnostic Imaging 299
8.4.3 Responsive Polymer-inorganic Hybrid Nanogels in Drug Delivery 301
References 306
9 Core/Shell Nanoparticles for Drug Delivery and Diagnosis 315
Hwanbum Lee, Jae Yeon Kim, Eun Hee Lee, Young In Park, Keun Sang Oh, Kwangmeyung Kim, Ick Chan Kwonand Soon Hong Yuk
9.2 Core/Shell NPs from Polymeric Micelles 319
9.2.1 Polymeric Micelles with Physical Drug Entrapment 319
9.2.2 Polymeric Micelles with Drug Conjugation 321
9.2.3 Polymeric Micelles Formed by Temperature-Induced Phase Transition 323
9.3 Phospholipid-based Core/Shell Nanoparticles 325
9.4 Layer-by-Layer-Assembled Core/Shell Nanoparticles 329
9.5 Core/Shell NPs for Diagnosis 330
9.4 Conclusions 331
Acknowledgments 331
References 331
10 Dendrimer Nanoparticles and Their Applications in Biomedicine 339
Arghya Paul, Wei Shao, Tom J. Burdon, Dominique Shum-Tim and Satya Prakash
10.1 Introduction 340
10.2 Dendrimers and Their Characteristics 341
10.3 Biomolecular Interactions of Dendrimer Nanocomplexes 343
10.3.1 Genes (siRNA/ANS/DNA) 344
10.3.2 Drugs and Pharmaceutics 345
10.4 PotentialApplications of Dendrimer in Nanomedicine 347
10.4.1 Delivery of Chemotherapeutics 347
10.4.2 Delivery of Biomolecules 348
10.4.3 Imaging 350
10.5 Conclusion 353
Acknowledgements 355
Indexing words 355
References 355
11 Theranostic Nanoparticles for Cancer Imaging and Therapy 363
Mami Murakami, Mark J. Ernsting and Shyh-Dar Li
11.1 Introduction 363
11.2 Multifunctional Nanoparticles for Noninvasive
11.2.1 Radiolabeled Nanoparticles 366
11.2.2 Fluorescence Imaging of Biodistribution 367
11.2.3 Multimodal Radiolabel and Fluorescence Imaging of Biodistribution 368
11.2.4 MRI Imaging of Biodistribution 369
11.2.5 Multimodal MRI and Fluorescence Imaging of Biodistribution 371
11.2.6 Multimodal Optical and CT Imaging of Biodistribution 372
11.2.7 Pharmacokinetics and Pharmacodynamics of Theranostics vs Diagnostics 373
11.3 Multifunctional Nanoparticles for Monitoring Drug Release 375
11.3.1 MRI imaging of Drug Release 375
11.3.2 Fluorescent Imaging of Drug Release 379
11.4 Theranostics to Image Therapeutic Response 380
11.5 Conclusion and Future Directions 382
Acknowledgement 383
References 383
Part IV: Nanoscaffolds technology
12 Nanostructure Polymers in Function Generating Substitute and Organ Transplants 389
S.K. Shukla
12.1 Introduction 389
12.2 Important Nanopolymers 391
12.2.1 Hydrogels 393
12.2.2 Bioceramics 394
12.2.3 Bioelastomers 395
12.2.4 Chitosan and Derivatives 396
12.2.5 Gelatine 396
12.3 MedicalApplications 397
12.3.1 Tissue Engineering for Function Generating 398
12.3.2 Tissue Engineering inArti¿cial Heart 400
12.3.3 Tissue Engineering in Nervous System 401
12.3.4 Bone Transplants 404
12.3.5 Kidney and Membrane Transplants 406
12.3.6 Miscellaneous 409
Acknowledgement 411
References 411
13 Electrospun Nanöberfor Three Dimensional Cell Culture 417
Yashpal Sharma, Ashutosh Tiwari and Hisatoshi Kobayashi
13.1 Introduction 417
13.2 Nanöber Scaffolds Fabrication Techniques 419
13.2.1 Self-Assembly 419
13.2.2 Phase Separation 421
13.2.3 Electrospinning 422
13.3 Parameters of Electrospinning Process 424
13.3.1 Viscosity or Concentration of the Polymeric Solution 424
13.3.2 Conductivity and the Charge Density 425
13.3.3 Molecular Weight of Polymer 425
13.3.4 Flow Rate 425
13.3.5 Distance from Tip to Collector 425
13.3.6 VoltageApplied 426
13.3.7 Environmental Factors 426
13.4 Electrospun Nanöbers for Three-dimensional Cell Culture 426
13.5 Conclusions 429
References 431
14 Magnetic Nanoparticles in Tissue Regeneration 435
Anuj Tripathi, Jose Savio Melo and Stanislaus Francis D'Souza
14.1 Introduction 435
14.2 Magnetic Nanoparticles: Physical Properties 438
14.3 Synthesis of Magnetic Nanoparticles 440
14.4 Design and Structure of Magnetic Nanoparticles 443
14.5 Stability and Functionalization of Magnetic Nanoparticles 445
14.6 Cellular Toxicity of Magnetic Nanoparticles 450
14.7 Tissue EngineeringApplications of Magnetic Nanoparticles 453
14.7.1 Magnetofection 455
14.7.2 Cell-patterning 458
14.7.3 Magnetic Force-induced Tissue Fabrication 461
14.8 Challenges and Future Prospects 473
Acknowledgement 474
References 474
15 Core-sheath Fibersfor Regenerative Medicine 485
Rajesh Vasita and Fabrizio Gelain
15.1 Introduction 486
15.1.1 Tissue Engineering 487
15.1.2 Scaffold Fabrication Technology 488
15.2 Core-sheath Nanöber Technology 489
15.2.1 Co-axial Electrospinning 491
15.2.2 Emulsion Electrospinning 501
15.2.3 Melt Co-axial Electrospinning 503
15.3Application of Core-sheath Nanöbers 504
15.3.1 Delivery of Bioactive Molecules 504
15.3.2 Tissue Engineering 513
15.4 Conclusions 519
References 519
