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