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Ajay Kumar Mishra is currently working as the Director at the Centre for Nanomaterials Science and also as an associate professor at the Department of Applied Chemistry, University of Johannesburg, South Africa, where he is a group leader of the research area for the composites/nanocomposites, water research, and bio-inorganic chemistry.
Part 1: Nanomedicine 1
1 High-technology Therapy Using Biomolecules or Synthetic Compounds for HIV Inhibition 3
Elvis Fosso-Kankeu, Pascaline Fontehand Ajay K.Mishra
1.1 Gene Therapy Including RNAHigh-Technology Against HIV 4
1.1.2 Antisense Sequences Technology 4
1.1.3 Ribozymes Technology 11
1.1.4 RNAInterference Technology 13
1.2 Metals and HIV Therapy 16
1.2.2 Metals and HIV 20
1.2.3 Nanotechnology and HIV 23
1.3 Conclusions 26
References 27
2 Emerging Nanomedicine Approaches for Osteochondral Tissue Regeneration 39
Author Lineis Missing
2.1 Introduction 39
2.1.1 Current Surgical Treatments 40
2.2 Emerging NanomedicineApproaches 42
2.2.1 Osteochondroconductive Scaffolds 43
2.2.2 Osteochondrogenic Precursor Cells 50
2.2.3 Osteochondroinductive Signals 51
References 54
3 Synthesis of Poly(Methacrylate) Encapsulated Magnetite Nanoparticles via Phosphonic Acid Anchoring Chemistry and Its Applications Toward Biomedicine 63
B. Kothandapaniand Ajay K. Mishra
3.1 Introduction 64
3.1.1 Magnetic Materials 65
3.1.2 Paramagnetism 66
3.1.3 Ferromagnetism 67
3.1.4 Superparamagnatism and Domain Walls 67
3.1.5 Polymer Brush 68
3.1.6 “Grafting to” Technique 69
3.1.7 “Grafting from” Technique 70
3.1.8 Immobilization of Initiators Using Various Anchoring Chemistry to Nanoparticles 71
3.2 Synthesis of Magnetite Nanoparticles 73
3.2.1 Immobilization ofATRPInitiator onto the Surface of MNs 75
3.2.2 Grafting of Polymer Brushes Using ImmobilizedATRPInitiator 78
3.2.3 Dispersion of MNs 80
3.3 Application in Biomedical Fields 82
3.3.2 Stem-cell Labeling 82
3.3.3 Gene Delivery 83
3.3.4 Drug Delivery 83
3.3.5 Bioseparation 84
3.4 Conclusions 84
References 85
4 Potentiometric PVC Membrane Sensors and Their Analytical Applications in Pharmaceuticals and Environmental Samples at Micro- and Nano-level 87
Gamal Abel-Hafiz Mostafa
4.1 Introduction 87
4.2 Ion Selective Electrode 88
4.3 Glass Membrane Electrode 89
4.3.1 Solid State Electrode 89
4.3.2 Liquid Membrane Electrode 89
4.4 Characteristics of ISE 90
4.4.2 Detection Limit 91
4.4.3 Response Time 91
4.4.4 Selectivity 91
4.4.5 Sensitivity 93
4.4.6 Lifetime 94
4.4.7 Accuracy and Precision 94
4.5 Preparation of PVC Membrane 94
4.5.2 ISE Membrane Components 94
4.5.3 The Polymeric Matrix 95
4.5.4 The Ionophore (Membrane-active Recognition) 95
4.5.5 The Membrane Solvent (Plasticizer) 95
4.5.6 IonicAdditives 96
4.6 Method of Preparation of the Liquid Membrane ISEs 96
4.6.2 Preparation of ISEs liquid Membranes 97
4.7 Application of Ion Selective Electrodes in Pharmaceutical and Environmental Analysis Using 97
4.7.1 Ion-pair as Electroactive Material 97
4.7.2 Ionophore as Electroactive Material 112
4.7.3 Schiff Base as Electroactive Material 116
4.8 Conclusion 123
References 127
5 Bioceramics: Silica-based Organic-Inorganic Hybrid Materials for Medical Applications 135
Sadanand Pandey and Shivani B. Mishra
5.1 Introduction 136
5.1.2 Definitionsof Biocompatibility 138
5.1.3 Properties ofAdvanced Bioceramics 140
5.2 Organic-Inorganic Hybrid Materials 141
5.3 Tissue Engineering 146
5.3.1 Strong Interactions via Covalent Linkages between 3D-Scaffolds and OsteoinductiveAgents 147
5.4 Other Organic-Inorganic Bioceramics for Medical Applications 150
5.4.1 Drug Delivery 151
5.5 Conclusion 156
5.6 Considerations and Future Directions 157
Acknowledgement 157
References 158
6 Recent Advances of Multifunctional Nanomedicines 163
Pradeep Pratap Singh and Ambika
6.1 Introduction 163
6.2 Nanomaterials of Biomedical Interest 164
6.3 Target-specificPharmacotherapy: Need for Nanocarrier Delivery Systems 165
6.4 Engineering of Pharmaceutical Nanosystems 166
6.4.1 Functional Nanosystems 166
6.4.2 Multifunctional Nanosystems 166
6.5 Applications of Pharmaceutical Nanotools 180
6.6 Nanotoxicity 181
6.7 Future prospects 182
6.8 Conclusion 183
References 184
7 Nanomedicinal Approaches for Diabetes Management 189
Prashant Kumar Raiand Ajay Kumar Mishra
7.1 Introduction: The Motivation behind the Chapter 189
7.2 Type of Diabetes 191
7.2.2 Type 2 or Non-Insulin-Dependent Diabetes Mellitus (NIDDM) 191
7.2.3 Type 3 Diabetes 191
7.3 Treatments for Diabetes 192
7.4 Why the Interest in Nanomedicine Research? 193
7.5 The Vision of Nanotechnology and its Clinical Applications for Diabetes 194
7.6 Summary 195
Acknowledgements 195
References 195
8 Polymeric Nanofibersin Regenerative Medicine 197
Narayan Chandra Mishra and Sharmistha Mitra (Majumder)
8.1 Introduction 197
8.2 Preparation of Nanofibers 199
8.3 RecentAdvances onApplication of Polymeric Nanofibersin Regenerative Medicine 201
8.3.2 Bone 204
8.3.3 Skin 206
8.3.4 Heart/Cardiac Grafts 208
8.3.5 Liver 210
8.3.6 Teeth 211
8.3.7 Ligament 212
8.3.8 Tendon 213
8.3.9 Cornea 214
8.3.10 Bladder 215
8.3.11 Blood vessel 215
8.3.12 Skeletal Muscle 218
8.3.13 Nerve 219
8.3.14 Esophagus 221
8.3.15 Adipose Tissue 221
8.3.16 Salivary Gland 221
8.4 Conclusions 222
References 222
Part 2: Drug Delivery and Therapeutics 227
9 Multifunctional Nano/Micro Polymer Capsules as Potential 229
Haider Sami, J. Jaishree, Ashok Kumar and Sri Sivakumar
9.1 Introduction 230
9.2 Synthesis of Polymer Capsules 232
9.2.1 Templated Synthesis 232
9.2.2 Templated Synthesis 233
9.3 Properties of Multilayered Polymer Capsules 237
9.4 Loading of Therapeutics 239
9.5 Stimuli-responsive Polymer Capsules 242
9.5.1 pH Responsive Polymer Capsules 243
9.5.2 Glucose Responsive Polymer Capsules 246
9.5.3 Redox responsive Polymer Capsules 248
9.5.4 Salt Responsive Polymer Capsules 249
9.5.5 Enzyme Responsive Polymer Capsules 249
9.5.6 Thermoresponsive Polymer Capsules 252
9.5.7 Ultrasound Responsive Polymer Capsules 253
9.5.8 Dual-responsive Polymer Capsules 254
9.6 Multifunctional Hybrid Capsules 255
9.6.1 Nanoparticles-modifiedCapsules 257
9.6.2 Capsosomes 266
9.7 Targeted Polymer Capsules 267
9.7.1 SpecificCell Targeting by Biomolecules 267
9.7.2 Magnetic Targeting 267
9.8 BiomedicalApplications 268
9.8.1 Drug Delivery 270
9.8.2 Bioimaging 271
9.8.3 Biosensing 272
9.9 Outlook and Future Prospects 274
References 274
10 Nanophosphors-Nanogold Immunoconjugates in Isolation of Biomembranes and in Drug Delivery 285
Dwijendra Gupta, Dhruv Kumar, Manish Dwivedi, Vijay Tripathi, Pratibha Phadke-Gupta and Surya Pratap Singh
10.1 Introduction 286
10.2 Nanoparticle Technology 287
10.3 The Versatility of Nanoparticles in Biological Sciences 288
10.3.1 The Biologic Problems – Why should We Study Them? 288
10.3.2 Lysosomal Storage Disorders 289
10.4 Materials and Methods 293
10.4.1 PreparationofNanogoldParticles(5–12nm) andNanogoldImmunoconjugates 293
10.4.2 Generating IgYs (against known cDNAs) in Layer Hens 293
10.4.3 Recombinant Constructs with DKFZp564K2464 (also known as Human Transmembrane protein TMEM22 (accession UGID: 692851) 294
10.4.4 Expression of Fusion Protein GFP-DKFZp564K2464 295
10.4.5 Metabolic Labeling Experiments 295
10.5 Nanotags for Bio-labeling and Targeting: Nanophosphors or Quantum Dots 297
10.5.1 Preparation of Nanophosphors 297
10.6 AFM Study of CdS and BSATagged ZnS-Mn Nanoparticles 302
10.6.2 AFM Imaging 302
10.6.3 AFM ImageAnalysis 304
10.7 Nano-Conjugates in Drug Delivery 304
10.8 Nanoparticle-mediated Drug Delivery and Nanotherapeutics 305
10.9 The Limitations of QDs 306
10.10 Summary 307
Acknowledgements 308
References 309
11 Cyclodextrin-based Nanoengineered Drug Delivery System 313
Jaya Lakkakula and Rui Werner Maçedo Krause
11.1 Introduction 314
11.2 Inclusion Complex Formation 316
11.3 Phase Solubility Relationships 318
11.4 Effect of Cyclodextrin on Drug Formulation 321
11.4.2 Effect on DrugAbsorption and Bioavailability 322
11.4.3 Effect on Drug Stability 323
11.5 Cyclodextrin-based Drug Delivery 324
11.5.1 Oral drug Delivery 326
11.5.2 Nasal Drug Delivery 328
11.5.3 Transdermal Drug Delivery 329
11.5.4 Ophthalmic Drug Delivery 330
11.6 Cyclodextrins in Novel Drug Delivery Systems (DDS) 331
11.6.1 Cyclodextrin in Nanoparticles 331
11.6.2 Liposomes 332
11.6.3 Microspheres 333
11.6.4 Hydrogels 334
11.7 Conclusion 335
Acknowledgements 335
References 338
12 Medicinal Patches and Drug Nanoencapsulation 343
María H. Lissarrague, Hernan Garate, Melisa E. Lamanna, Norma B. D’Accorso and Silvia N.Goyanes
12.1 Introduction 343
12.2 Overview of Passive Skin Permeation (Passive Patches) 344
12.2.1 Human Skin 345
12.2.2 Transdermal Passive Patches 347
12.3 Recent Development on Skin Permeation 357
12.3.1 Passive Permeation Enhancement 358
12.3.2 TransdermalActive Patches 359
12.4 Drug Encapsulation 361
12.4.1 Production of Polymer-based Nanoparticulate Drug Delivery 362
12.4.2 Production of Natural Organic and Protein-based Nanoparticulate Drug Delivery 365
12.4.3 Production of Nanoparticles from Natural Macromolecules: Chitosan Nanoparticles 366
12.4.4 Drug Loading 367
12.5 Triggered Release 369
12.5.1 External Stimuli 370
12.5.2 Transdermal Delivery 373
12.6 Conclusions 374
References 374
13 Dendrimers: AClass of Polymer in the Nanotechnology for the Drug Delivery 379
Sunil K.Singh and Vivek K. Sharma
13.1 Introduction 379
13.2 Historical Origin of Dendrimers 380
13.3 Structure of Dendrimers 381
13.4 Terms Used in Dendrimer Chemistry 383
13.5 Types of Dendrimers 385
13.5.1 Chiral Dendrimers 385
13.5.2 Liquid Crystalline Dendrimers 385
13.5.3 Tecto Dendrimers 386
13.5.4 PAMAM Dendrimers 386
13.5.5 PPI Dendrimers 387
13.5.6 Hybrid Dendrimers 389
13.5.7 Peptide Dendrimers 390
13.5.8 Glycodendrimers 390
13.6 Application of Dendrimers 392
13.6.1 Dendrimers as a Carrier for Drug Delivery 392
13.7 Dendrimers in Oral Drug Delivery 394
13.8 Dendrimers in Transdermal Drug Delivery 396
13.9 Dendrimers in Ocular Drug Delivery 398
13.10 Dendrimers inAnticancer Drug Delivery 399
13.11 Dendrimers in Cancer Diagnosis and Treatment 401
13.11.1 Diagnosis 401
13.11.2 Targeting 403
13.11.3 Treatment 404
13.11.4 Photodynamic Therapy 406
13.11.5 Photothermal Therapy 408
13.11.6 Gene Transfection 408
13.11.7 BoronNeutronCaptureTheraphy(BNCT) 410
13.12 Conclusion 411
References 411
14 Designing Nanocarriers for Drug Delivery 417
Munishwar N. Gupta and Joyeeta Mukherjee
14.1 Introduction 417
14.2 Sizes, Shapes andAdvantages of Nanomaterials 418
14.3 Bioconjugation Strategies 421
14.3.1 Modifying with Polymers 427
14.4 Carbon Nanotubes 429
14.4.1 Noncovalent Functionalization 430
14.4.2 Covalent Functionalization 432
14.5 Drug Targeting 434
14.6 Future Perspectives 436
Acknowledgements 437
References 437
15 Multifunctional Polymeric Micelles for Drug Delivery and Therapeutics 443
Alicia Sawdon and Ching-An Peng
15.1 Introduction 443
15.2 Composition, Formation and Characterization of Polymeric Micelles 444
15.2.1 Polymeric Micelle Formation 445
15.2.2 Preparation of Polymeric Micelles 448
15.2.3 FactorsAffecting Drug Loading and Drug Release from Polymeric Micelles 449
15.3 Polymeric Micelles for Cancer Chemotherapy 450
15.3.1 Biological Significance 450
15.3.2 Passive Targeting 452
15.3.3 Polymeric Micelles in Clinical Trials 452
15.4 Targeting Schemes 457
15.4.1 Active Targeting 458
15.4.2 Angiogenesis-associated Targeting 459
15.4.3 Uncontrolled Cell Proliferation Targeting 460
15.4.4 Stimuli-Sensitivity 463
15.5 Polymeric Micelles for Diagnostics and Imaging 465
15.5.1 Diagnostics 465
15.5.2 Imaging 466
15.6 Conclusions 467
References 467
16 Nanoparticles-based Carriers for Gene Therapy and Drug Delivery 477
Marketa Ryvolova, Jana Drbohlavova, Kristyna Smerkova, Jana Chomoucka, Pavlina Sobrova,Vojtech Adam, PavelKopel, Jaromir Hubalek and Rene Kizek
16.1 Introduction 478
16.2 Targeted Delivery 478
16.2.1 Gene Delivery 479
16.2.2 Drug Delivery 482
16.3 Conclusion 494
References 494
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