Nanomaterials in Drug Delivery, Imaging, and Tissue Engineering

Ashutosh Tiwari is an assistant professor of nanobioelectronics at the Biosensors and Bioelectronics Centre, IFM-Linköping University, Editor-in-Chief of Advanced Materials Letters, and a materials chemist. He graduated from the University of Allahabad, India. He has published more than 125 articles and patents as well as authored/edited in the field of materials science and technology. Dr.Tiwari received the 2011 "Innovation in Materials Science Award and Medal" during the International Conference on Chemistry for Mankind: Innovative Ideas in Life Sciences.Atul Tiwari is an associate researcher at the Department of Mechanical Engineering in the University of Hawaii, USA. He received his PhD in Polymer Science and earned the Chartered Chemist and Chartered Scientist status from the Royal Society of Chemistry, UK. His areas of research interest include the development of silicones and graphene materials for various industrial applications. Dr. Tiwari has invented several international patents pending technologies that have been transferred to industries. He has been actively engaged in various fields of polymer science, engineering, and technology and has published more than fifty peer-reviewed journal papers, book chapters, and books related to material science.

• Preface xv Part I: Biomedical nanomaterials1 Nanoemulsions: Preparation, Stability and Application in Biosciences 1Thomas Delmas, Nicolas Atrux-Tallau, Mathieu Goutayer, SangHoon Han, Jin Woong Kim, and Jérôme Bibette1.1 Introduction 21.2 Nanoemulsion:A Thermodynamic Definition and Its Practical Implications 51.2.1 Generalities on Emulsions 51.2.2 Nanoemulsion vs. Microemulsion, a Thermodynamic Definition 61.3 Stable Nanoemulsion Formulation 91.3.1 Nanoemulsion Production 91.3.2 Nanoemulsion Stability Rules 111.3.3 Nanoemulsion Formulation Domain 161.3.4 Conclusion on the Formulation of Stable Nanoemulsions 211.4 Nanoencapsulation in Lipid Nanoparticles 211.4.1 Aim ofActive Encapsulation 211.4.2 Lipid Complexity and Influence of Their Physical State 231.4.3 Amorphous Lipids for a Large Range of Encapsulated Molecules 271.4.4 Lipids Viscosity and Release 311.4.5 Conclusion on the Use ofAmorphous Lipid Matrices for Control OverActive Encapsulation and Release 341.5 Interactions between Nanoemulsions and the Biological Medium: Applications in Biosciences 351.5.1 Nanoemulsion Biocompatibility 351.5.2 Classical TargetingApproach by Chemical Grafting – Example of Tumor Cell Targeting by Crgd Peptide for Cancer Diagnosis and Therapy 381.5.3 New ‘No Synthesis Chemistry’Approach – Example of Pal-KTTKS andAsiaticoside Targeting for CosmeticActives Delivery 411.5.4 Conclusion on Nanoemulsions Application in Biosciences 461.6 General Conclusion 47References 482 Multifunctional Polymeric Nanostructures for Therapy and Diagnosis 57Angel Contreras-García and Emilio Bucio2.1 Introduction 582.2 Polymeric-based Core-shell Colloid 612.3 Proteins and Peptides 642.4 Drug Conjugates and Complexes with Synthetic Polymers 652.5 Dendrimers, Vesicles, and Micelles 672.5.1 Dendrimers 672.5.2 Vesicles 682.5.3 Micelles 702.6 Smart Nanopolymers 712.6.1 Temperature and pH Stimuli-responsive Nanopolymers 722.6.2 Hydrogels 722.6.3 Stimuli Responsive Biomaterials 732.6.4 Interpenetrating Polymer Networks 742.7 Stimuli Responsive Polymer-metal Nanocomposites  752.8 Enzyme-responsive Nanoparticles 78Acknowledgements 83References 833 Carbon Nanotubes: Nanotoxicity Testing and Bioapplications 97R. Sharma and S. Kwon3.1 Introduction 983.1.1 What is Nanotoxicity of Nanomaterials? 983.2 Historical Review of Carbon Nanotube 993.3 Carbon Nanotubes (CNTs) and Other Carbon Nanomaterials 1003.3.1 Physical Principles of Carbon Nanotube Surface Science 1023.4 Motivation – Combining Nanotechnology and Surface Science with Growing Bioapplications 1043.5 Cytotoxicity Measurement and Mechanisms of CNT Toxicity 1113.1.6 In Vivo Studies on CNT Toxicity 1133.1.7 Inflammatory Mechanism of CNT Cytoxicity 1143.1.8 Characterization and Toxicity of SWCNT and MWCNT Carbon Nanotubes 1163.6 MSCs Differentiation and Proliferation on Different Types of Scaffolds 1203.6.1 An In Vivo Model CNT-Induced Inflammatory Response in Alveolar Co-culture System 1223.6.2 Static Model: 3-Dimensional Tissue Engineered Lung 1243.6.3 Dynamic Model: Integration of 3D Engineered Tissues into Cyclic Mechanical Strain Device 1263.6.4 In Vivo MR Microimaging Technique of Rat Skin Exposed to CNT 1273.7 New Lessons on CNT Nanocomposites 1303.8 Conclusions 135Part II: Advanced nanomedicine4 Discrete Metalla-Assemblies as Drug Delivery Vectors 149Bruno Therrien4.1 Introduction 1494.2 Complex-in-a-Complex Systems 1504.3 Encapsulation of Pyrenyl-functionalized Derivatives 1554.4 Exploiting the Enhanced Permeability and Retention Effect 1594.5 Incorporation of Photosensitizers in Metalla-assemblies 1624.6 Conclusion 165Acknowledgments 165References 1665 Nanomaterials for Management of Lung Disorders and Drug Delivery 169Jyothi U. Menon, Aniket S. Wadajkar, Zhiwe iXie, and Kytai T. Nguyen5.1 Lung Structure and Physiology 1705.2 Common Lung DiseasesAnd Treatment Methods 1715.2.1 Lung Cancer 1715.2.2 PulmonaryArterial Hypertension 1725.2.3 Obstructive Lung Diseases 1735.3 Types of Nanoparticles (NPs) 1735.3.1 Liposomes 1745.3.2 Micelles 1765.3.3 Dendrimers 1775.3.4 Polymeric Micro/Nanoparticles 1775.4 Methods for Pulmonary Delivery 1795.4.1 Nebulization 1795.4.2 Metered Dose Inhalation (MDI) 1825.4.3 Dry Powder Inhalation (DPI) 1835.4.4 IntratrachealAdministration 1835.5 Targeting Mechanisms 1845.5.1 Passive Targeting 1845.5.2 Active Targeting 1855.5.3 Cellular Uptake Mechanisms 1885.6 TherapeuticAgents Used for Delivery 1885.6.1 ChemotherapeuticAgents 1885.6.2 Bioactive Molecules 1905.6.3 Combinational Therapy 1905.7 Applications 1915.7.1 Imaging/DiagnosticApplications 1915.7.2 TherapeuticApplications 1935.7.3 Lung Remodeling and Regeneration 1945.8 Design Considerations of NPs 1955.8.1 Half-life of NPs 1955.8.2 Drug Release Mechanisms 1955.8.3 Clearance Mechanisms in the Lung 1965.9 Current Challenges and Future Outlook 1976 Nano-Sized Calcium Phosphate (CaP) Carriers for Non-Viral Gene/Drug Delivery 199Donghyun Lee, Geunseon Ahn and Prashant N. Kumta6.1 Introduction 2006.2 Vectors for Gene Delivery 2026.2.1 Viral Vectors 2036.2.2 Non-viral Vectors 2036.2.3 Calcium Phosphate Vectors 2056.3 Modulation of Protection and Release Characteristics of Calcium Phosphate Vector 2136.4 Calcium Phosphate Carriers for Drug Delivery Systems 2196.4.1 Antibiotics Delivery 2196.4.2 Growth Factor Delivery 2216.5 Variants of Nano-calcium Phosphates: Future Trends of the CaPDelivery Systems 221Acknowledgements 223References 2237 Organics ModifiedMesoporous Silica for Controlled Drug Delivery Systems 233Jingke Fu, Yang Zhao, Yingchun Zhu and Fang Chen7.1 Introduction 2337.2 Controlled Drug Delivery Systems Based on Organics Modified7.2.1 MSNs-based Drug Delivery Systems Controlled by Physical Stimuli 2387.2.2 MSNs-based Drug Delivery Systems Controlled by Chemical Stimuli 2467.3 Conclusions 258References 259Part III: Nanotheragnostics8 Responsive Polymer-Inorganic Hybrid Nanogels for Optical Sensing, Imaging, and Drug Delivery 263Weitai Wu and Shuiqin Zhou8.1 Introduction 2648.2 Mechanisms of Response 2688.2.1 Reception of an External Signal 2688.2.2 Volume Phase Transition of the Hybrid Nanogels 2758.2.4 Regulated Drug Delivery 2828.3 Synthesis of Responsive Polymer-inorganic Hybrid Nanogels 2858.3.1 Synthesis of the Hybrid Nanogels from Pre-synthesized Polymer Nanogels 2858.3.2 Synthesis of the Hybrid Nanogels from Pre-synthesized Inorganic NPs 2898.3.3 Synthesis of the Hybrid Nanogels by a Heterogeneous Polymerization Method 2928.4 Applications 2938.4.1 Responsive Polymer-inorganic Hybrid Nanogels in Optical Sensing 2938.4.2 Responsive Polymer-inorganic Hybrid Nanogels in Diagnostic Imaging 2998.4.3 Responsive Polymer-inorganic Hybrid Nanogels in Drug Delivery 301References 3069 Core/Shell Nanoparticles for Drug Delivery and Diagnosis 315Hwanbum Lee, Jae Yeon Kim, Eun Hee Lee, Young In Park, Keun Sang Oh, Kwangmeyung Kim, Ick Chan Kwonand Soon Hong Yuk9.2 Core/Shell NPs from Polymeric Micelles 3199.2.1 Polymeric Micelles with Physical Drug Entrapment 3199.2.2 Polymeric Micelles with Drug Conjugation 3219.2.3 Polymeric Micelles Formed by Temperature-Induced Phase Transition 3239.3 Phospholipid-based Core/Shell Nanoparticles 3259.4 Layer-by-Layer-Assembled Core/Shell Nanoparticles 3299.5 Core/Shell NPs for Diagnosis 3309.4 Conclusions 331Acknowledgments 331References 33110 Dendrimer Nanoparticles and Their Applications in Biomedicine 339Arghya Paul, Wei Shao, Tom J. Burdon, Dominique Shum-Tim and Satya Prakash10.1  Introduction 34010.2  Dendrimers and Their Characteristics 34110.3  Biomolecular Interactions of Dendrimer Nanocomplexes 34310.3.1  Genes (siRNA/ANS/DNA) 34410.3.2  Drugs and Pharmaceutics 34510.4  PotentialApplications of Dendrimer in Nanomedicine 34710.4.1  Delivery of Chemotherapeutics 34710.4.2  Delivery of Biomolecules 34810.4.3  Imaging 35010.5  Conclusion 353Acknowledgements 355Indexing words 355References 35511 Theranostic Nanoparticles for Cancer Imaging and Therapy 363Mami Murakami, Mark J. Ernsting and Shyh-Dar Li11.1  Introduction 36311.2  Multifunctional Nanoparticles for Noninvasive11.2.1 Radiolabeled Nanoparticles 36611.2.2 Fluorescence Imaging of Biodistribution 36711.2.3 Multimodal Radiolabel and Fluorescence Imaging of Biodistribution 36811.2.4 MRI Imaging of Biodistribution 36911.2.5 Multimodal MRI and Fluorescence Imaging of Biodistribution 37111.2.6 Multimodal Optical and CT Imaging of Biodistribution 37211.2.7 Pharmacokinetics and Pharmacodynamics of Theranostics vs Diagnostics 37311.3  Multifunctional Nanoparticles for Monitoring Drug Release 37511.3.1 MRI imaging of Drug Release 37511.3.2 Fluorescent Imaging of Drug Release 37911.4  Theranostics to Image Therapeutic Response 38011.5  Conclusion and Future Directions 382Acknowledgement 383References 383Part IV: Nanoscaffolds technology12 Nanostructure Polymers in Function Generating Substitute and Organ Transplants 389S.K. Shukla12.1  Introduction 38912.2  Important Nanopolymers 39112.2.1 Hydrogels 39312.2.2 Bioceramics 39412.2.3 Bioelastomers 39512.2.4 Chitosan and Derivatives 39612.2.5 Gelatine 39612.3  MedicalApplications 39712.3.1 Tissue Engineering for Function Generating 39812.3.2 Tissue Engineering inArtificial Heart 40012.3.3 Tissue Engineering in Nervous System 40112.3.4 Bone Transplants 40412.3.5 Kidney and Membrane Transplants 40612.3.6 Miscellaneous 409Acknowledgement 411References 41113 Electrospun Nanofiberfor Three Dimensional Cell Culture 417Yashpal Sharma, Ashutosh Tiwari and Hisatoshi Kobayashi13.1  Introduction 41713.2  Nanofiber Scaffolds Fabrication Techniques 41913.2.1 Self-Assembly 41913.2.2 Phase Separation 42113.2.3 Electrospinning 42213.3  Parameters of Electrospinning Process 42413.3.1 Viscosity or Concentration of the Polymeric Solution 42413.3.2 Conductivity and the Charge Density 42513.3.3 Molecular Weight of Polymer 42513.3.4 Flow Rate 42513.3.5 Distance from Tip to Collector 42513.3.6 VoltageApplied 42613.3.7 Environmental Factors 42613.4  Electrospun Nanofibers for Three-dimensional Cell Culture 42613.5  Conclusions 429References 43114 Magnetic Nanoparticles in Tissue Regeneration 435Anuj Tripathi, Jose Savio Melo and Stanislaus Francis D’Souza14.1  Introduction 43514.2  Magnetic Nanoparticles: Physical Properties 43814.3  Synthesis of Magnetic Nanoparticles 44014.4  Design and Structure of Magnetic Nanoparticles 44314.5  Stability and Functionalization of Magnetic Nanoparticles 44514.6  Cellular Toxicity of Magnetic Nanoparticles 45014.7  Tissue EngineeringApplications of Magnetic Nanoparticles 45314.7.1 Magnetofection 45514.7.2 Cell-patterning 45814.7.3 Magnetic Force-induced Tissue Fabrication 46114.8  Challenges and Future Prospects 473Acknowledgement 474References 47415 Core-sheath Fibersfor Regenerative Medicine 485Rajesh Vasita and Fabrizio Gelain15.1  Introduction 48615.1.1 Tissue Engineering 48715.1.2 Scaffold Fabrication Technology 48815.2  Core-sheath Nanofiber Technology 48915.2.1 Co-axial Electrospinning 49115.2.2 Emulsion Electrospinning 50115.2.3 Melt Co-axial Electrospinning 50315.3Application of Core-sheath Nanofibers 50415.3.1 Delivery of Bioactive Molecules 50415.3.2 Tissue Engineering 51315.4  Conclusions 519References 519

“The volume was written by many scientists working in the new area of nanotechnology. Each chapter has an extensive reference list and there is a short index at the end.”  (Optics & Photonics News, 22 November 2013)