Discover thorough insights into the toxicology of nanomaterials used in medicine
In Nanotechnology in Medicine: Toxicity and Safety, an expert team of nanotechnologists delivers a robust and up-to-date review of current and future applications of nanotechnology in medicine with a special focus on neurodegenerative diseases, cancer, diagnostics, nano-nutraceuticals, dermatology, and gene therapy. The editors offer resources that address nanomaterial safety, which tends to be the greatest hurdle to obtaining the benefits of nanomedicine in healthcare.
The book is a one-stop resource for recent and comprehensive information on the toxico logical and safety aspects of nanotechnology used in human health and medicine. It provides readers with cutting-edge techniques for delivering therapeutic agents into targeted cellular compartments, cells, tissues, and organs by using nanoparticulate carriers. The book also offers methodological considerations for toxicity, safety, and risk assessment.
Nanotechnology in Medicine: Toxicity and Safety also provides readers with: - A thorough introduction to the nanotoxicological aspects of nanomedicine, including translational nanomedicine and nanomedicine personalization - Comprehensive introductions to nanoparticle toxicity and safety, including selenium nanoparticles and metallic nanoparticles - Practical discussions of nanotoxicology and drug delivery, including gene delivery using nanocarriers and the use of nanomaterials for ocular delivery applications - In-depth examinations of nanotechnology ethics and the regulatory framework of nanotechnology and medicine
Perfect for researchers, post-doctoral candidates, and specialists in the fields of nanotechnology, nanomaterials, and nanocarriers, Nanotechnology in Medicine: Toxicity and Safety will also prove to be an indispensable part of the libraries of nanoengineering, nanomedicine, and biopharmaceutical professionals and nanobiotechnologists.
Table of Contents
Preface xiii
List of Contributors xv
List of Abbreviations xix
Part I Nanomedicine: Nanotoxicological Insights 1
1 Nanomedicines: Applications and Toxicological Concerns 3
Mrunali Patel, Rashmin Patel, and Mahendra Rai
1.1 Introduction 3
1.2 Nanomedicine’s Revolution 9
1.3 Potential Applications of Nanomedicine 10
1.3.1 Diagnosis 10
1.3.2 Drug Delivery 12
1.3.3 Tissue Engineering and Regenerative Medicine 17
1.4 Clinical Translation of Nanomedicine 18
1.5 Nanotoxicological Challenges 19
1.6 Safety Issues and Regulations 22
1.7 Conclusion and Future Perspectives 23
References 24
2 Microbial Biopolymers and Their Derivatives as Nanotechnological Tools for Medicine:
Applications, Advantages, Toxicity, and Safety 29
Paulo Ricardo Franco Marcelino, Fernanda Gonçalves, Nayelen Sayuri Aizawa, Henrique Paiva
Pereira, Talita Martins Lacerda, and Silvio Silvério da Silva
2.1 Introduction 29
2.2 Natural Polymers: Conceptualization, Classifications, and Physicochemical Characteristics 30
2.3 Applications of Biopolymers in Nanoparticles, Nanofibers, and Drug Delivery Systems of Therapeutic Importance 35
2.4 Safety of Microbial Biopolymers Used in Nanoscale-Systems for Therapeutic Applications 38
2.5 Conclusions 40
References 41
Part II Nanoparticles: Toxicity and Safety 47
3 Selenium Nanoparticles: Toxicity and Safety 49
Irina A. Shurygina, Irina S. Trukhan, Nataliya N. Dremina, and Michael G. Shurygin
3.1 Introduction 49
3.2 Selenium Forms 50
3.3 Toxicity of Selenium Nanoparticles 52
3.4 Toxicity Mechanisms 56
3.5 Conclusion 60
References 60
4 Impact of Nanoparticles on Protozoa 67
Daniela Plachá and Josef Jampílek
4.1 Introduction 67
4.1.1 Antiprotozoal Drugs 72
4.2 Nanosystems 74
4.2.1 Preparation and Synthesis of Nanoparticles and Systems 75
4.3 Nanosystems with Effect on Human Parasitic Protozoa 77
4.3.1 Malaria 77
4.3.2 Trypanosomiases 79
4.3.3 Leishmaniasis 81
4.3.4 Toxoplasmosis 87
4.3.5 Cryptosporidium 89
4.3.6 Acanthamoeba 90
4.4 Nanosystems with Effect on Veterinary Parasitic Protozoa 91
4.5 Nanomaterial Toxicity on Beneficial Protozoa 93
4.6 Conclusion 96
Acknowledgment 97
References 97
5 Toxicity of Metallic Nanoparticles: A Pressing Issue 109
Tejal Mehta, Dhaivat Parikh, Kartik Hariharan, Namdev Dhas, and Viral Patel
5.1 Introduction 109
5.2 Toxicity of Metal Nanoparticles and Influence of Physicochemical Properties 110
5.2.1 Toxicity of Copper and Copper Oxide Nanoparticles 110
5.2.2 Toxicity of Gold Nanoparticles 112
5.2.2.1 Physicochemical Factors Influencing AuNPs’ Toxicity 112
5.2.3 Toxicity of Silver Nanoparticles 115
5.2.4 Toxicity of Zinc Oxide Nanoparticles 117
5.2.5 Toxicity of Iron Oxide Nanoparticles 118
5.2.6 Physicochemical Properties Affecting Toxicity 119
5.3 Accumulation and Toxicity of Metal-Based Nanoparticles in Various Organs 119
5.4 Conclusion and Future Perspectives 128
Acknowledgment 128
References 128
6 Toxicity, Safety, and Biodistribution of Multifunctional Mesoporous Silica
Nanoparticles 137
Mansi Athalye, Rashmin Patel, and Mrunali Patel
6.1 Introduction 137
6.2 Bioapplicability of Mesoporous Silica Nanoparticles 138
6.3 Biodistribution, Toxicity, and Safety of MSN 139
6.3.1 Factors Affecting Biodistribution of Mesoporous Silica Nanoparticles 140
6.3.1.1 Particle Size 140
6.3.1.2 Particle Shape 142
6.3.1.3 Functionalization 142
6.3.1.4 Dose 144
6.3.1.5 Route of Administration 145
6.4 Safety Evaluation of Mesoporous Silica Nanoparticles 145
6.4.1 Cytotoxicity 146
6.4.2 Tissue Compatibility 147
6.4.3 Genotoxicity 147
6.4.4 Immunotoxicity 148
6.4.5 Autophagy 148
6.4.6 Endothelial Dysfunction and Toxic Effects on Blood Cells 149
6.4.7 Blood Compatibility 149
6.4.8 Neurotoxicity 149
6.5 Conclusion and Future Directions 149
References 153
7 Safety and Toxicity Issues of Polymeric Nanoparticles: A Serious Concern 156
Priya Patel, Naimish Vyas, and Mihir Raval
7.1 Introduction 156
7.2 Application of Nanomaterials 157
7.3 Classification of Nanoparticles (NPs) 157
7.3.1 Polymeric Nanoparticles 158
7.3.1.1 Advantages of Polymeric Nanoparticles 159
7.3.1.2 Polymers Used in the Preparation of Polymeric Nanoparticles 159
7.3.1.3 Methods of Preparation of Polymeric Nanoparticles 160
7.3.1.4 Polymeric Nanoparticles in Drug Delivery 162
7.4 Nanotoxicology 163
7.4.1 Toxicity of Nanoparticles 163
7.4.2 Tissue Toxicity of Nanomedicine 164
7.4.3 Mechanisms of Nanoparticle Toxicity 164
7.4.4 Toxicity of Polymeric Nanoparticles 164
7.4.5 Nanoformulations Showing Toxicity 165
7.5 Safety Assessment of Nanomedicines by Methodological Considerations 167
7.5.1 Nanoparticles Safety Study 168
7.5.2 Methodological Considerations for Safety Assessment of Nanomedicines 169
7.6 Conclusion and Future Perspectives 170
References 170
8 Green Synthesis of Copper and Copper-Based Nanoparticles for Their Use in Medicine: Toxicity and Safety 174
Sadhucharan Mallick and Piyali Sabui
8.1 Introduction 174
8.2 Green Synthesis Methods of Copper and Copper-Based Nanoparticles 176
8.2.1 Fungi-Assisted Synthesis of Nanoparticles 176
8.2.2 Actinomycetes-Assisted Synthesis of Nanoparticles 176
8.2.3 Bacteria-Assisted Synthesis of Nanoparticles 177
8.2.4 Algae-Assisted Synthesis of Nanoparticles 177
8.2.5 Phytochemical-Assisted Synthesis of Nanoparticles 177
8.2.6 Biomolecule and Biopolymer-Mediated Synthesis of Nanoparticles 178
8.3 Purification of Copper and Copper-Based Nanoparticles 179
8.4 Characterization of Green Synthesized Copper and Copper-Based Nanoparticles 179
8.5 Copper and Copper-Based Nanoparticles as Nanomedicines 179
8.5.1 Application as Antibacterial Agents 179
8.5.2 Application as Antifungal Agents 182
8.5.3 Application as Antiviral Agents 182
8.5.4 Application as a Targeted Drug Delivery System 182
8.5.5 Application as Anticancer Agents 183
8.5.6 Applications in Molecular Imaging 184
8.6 Copper and Copper-Based Nanoparticles and Their Toxicity 184
8.6.1 Nanotoxicology 184
8.6.2 Different Types of Toxicity 185
8.6.3 Toxicity Effect of Copper and Copper-Based Nanoparticles 185
8.7 Safety Implications of Copper and Copper-Based Nanoparticles 186
8.8 Future Perspectives 187
8.9 Conclusion 188
References 189
Part III Nanotoxicology and Drug Delivery 195
9 Gene Delivery Using Nanocarriers: Toxicity and Safety Aspects 197
Imran Vhora and Nirav Khatri
9.1 Introduction 197
9.2 Nanocarrier Types 198
9.2.1 Lipid-Based Nanocarriers 198
9.2.2 Polymeric Nanocarriers 200
9.3 Target Diseases and Routes of Administration 200
9.4 Learnings from Clinical Trials 214
9.4.1 Toxicity with Systemic Delivery - Intravenous Administration 215
9.4.2 Toxicity with Local Delivery 215
9.4.2.1 Pulmonary Delivery 216
9.4.2.2 Intratumoral and Other Local Delivery in Cancer 216
9.4.2.3 Subcutaneous, Intradermal, and Intramuscular Delivery 216
9.5 Mechanisms of Toxicity of Gene Delivery Nanocarriers 217
9.5.1 Cellular Damage and Inflammatory Mediators 217
9.5.2 ROS Induction 219
9.5.2.1 Off-target Effects of the Genetic Cargo 219
9.6 Overcoming Toxicity Issues with Nanocarrier-Mediated Gene Therapy 220
9.6.1 Modification of Genetic Cargoes 220
9.6.2 Modification of Nanocarrier System 220
9.6.2.1 Optimizing Excipient Chemistry - Lipid and Polymer Chemistry 220
9.6.2.2 Modification of Nanocarrier Morphology 222
9.6.3 Preclinical Testing for Expected Toxicities 223
9.7 Future Perspectives and Conclusion 225
References 226
10 Toxicity and Safety Evaluation of Lipid-Based Nanoparticles for Brain Delivery 233
Mitali Patel and Priyanshi Patel
10.1 Introduction 233
10.2 Barriers Across Brain Delivery 234
10.2.1 The Blood-Brain Barrier (BBB) 234
10.2.2 The Blood Cerebrospinal Fluid (BCSF) Barrier 234
10.3 Role of Lipid Nanoparticles in Brain Delivery 235
10.3.1 Liposomes 236
10.3.2 Solid Lipid Nanoparticles (SLNs) 236
10.3.3 Nanostructured Lipid Carriers (NLCs) 237
10.3.4 Lipid-Drug Conjugates (LDCs) 237
10.3.5 Lipid Polymer Hybrid Nanoparticles (LPHNPs) 238
10.4 Transport Mechanisms Involved for Brain Delivery 238
10.4.1 Paracellular Transport 238
10.4.2 Transcellular Transport 238
10.4.3 Carrier-mediated Transport 238
10.4.4 Receptor-mediated Endocytosis 238
10.4.5 Adsorptive-mediated Endocytosis 239
10.5 Toxicity of Lipid Nanoparticles 239
10.6 Safety of Lipid Nanoparticles 240
10.7 Conclusion and Future Perspectives 242
References 242
11 Risk Assessment of Injectable Nanoparticles Used as Nanomedicine 248
Marco Vinícius Chaud, Fernando Batain, Eliana Barbosa Souto, Patrícia Severino, Aleksandra
Zielińska, and Thais Francine Ribeiro Alves
11.1 Introduction 248
11.2 Nanomaterials, Nanoparticles, and Nanoformulation 249
11.3 Injectable Nanoparticles Toxicity 251
11.4 Safety of Nanoparticles in Acute and Chronic Studies 253
11.5 Future Perspectives and Conclusion 254
References 255
12 Dermatological Delivery of Nanodrugs: Applications, Toxicity, and Safety 259
Saurabh Shivalkar, Arushi Verma, Vishal Singh, and Amaresh Kumar Sahoo
12.1 Introduction 259
12.2 An Overview of Dermatology and Nanodrugs 260
12.3 Nanomaterials for Dermatologically Active Nanodrugs 262
12.4 Nanoformulations for Topical and Transdermal Delivery 265
12.5 Applications of Dermatological Nanodrugs and Its Delivery Mechanisms 268
12.5.1 Prevention 268
12.5.1.1 Antisepsis 268
12.5.1.2 Cosmetics and Photoprotection 269
12.5.2 Diagnosis 269
12.5.3 Therapeutic Applications 270
12.5.3.1 Phototherapy 270
12.5.3.2 Sebaceous Gland Disorders 270
12.5.3.3 Treatment of Inflammatory Skin Diseases 270
12.5.3.4 Other Therapeutic Applications 270
12.6 Toxicity Evaluation of Dermatologically Active Nanodrugs 271
12.6.1 Nanodrugs and Toxicity Due to Penetration 271
12.6.2 Genotoxicity 273
12.7 Safety Considerations 273
12.8 Limitations and Risk 274
12.9 Conclusion 274
References 275
13 Nanonutraceuticals: Considerations for Toxicity and Safety Assessment 281
Shah Esha Bhavin and Anuradha Ketan Gajjar
13.1 Introduction 281
13.2 Novel Carrier-Based Drug Delivery Systems 282
13.2.1 Lipidic Nanosystems 283
13.2.1.1 Non-Vesicular Systems 283
13.2.1.2 Vesicular Systems 283
13.2.2 Polymeric Nanosystems 283
13.2.3 Lipid Polymer Nanosystems 285
13.3 Safety and Toxicity Assessment of Nanoparticles 285
13.4 Approaches for Biodegradable Nanoparticles 289
13.5 Modified Nanocarriers (Nanosponges) 291
13.5.1 Cyclodextrin-Based Nanosponges 291
13.6 Conclusion and Future Perspectives 293
References 293
14 Current Challenges and Future Needs for Nanotoxicity and Nanosafety Assessment 299
Ravish J. Patel, Amit Alexander, Anu Puri, and Bappaditya Chatterjee
14.1 Introduction 299
14.2 Nanomaterials: Risk Assessment 302
14.3 The Hurdles in Toxicity Evaluation of Nanomaterials 304
14.3.1 Physicochemical Properties of Nanomaterials’ Characterization 304
14.3.1.1 Size of Nanomaterials 304
14.3.1.2 Composition Effects 304
14.3.1.3 Surface-Related Effects 304 Agglomeration 305
14.3.1.5 Solubility 305
14.3.1.6 Surface Charge and Dispersity 305
14.3.1.7 Dose Metric 305
14.3.2 In vitro, In vivo, and In silico Approaches for the Assessment of Toxicity for the Nanomaterials 305
14.4 Nanosafety Assessment Tools 307
14.5 Conclusion and Perspectives 308
References 310
Part IV Nanotechnology, Ethics, and Regulatory Framework 315
15 Safety Regulations for the Use of Nanotechnological Products for Biomedical Applications: A Systematic Literature Review 317
Raquel Von Hohendorff, Wilson Engelmann, and Daniele Weber S. Leal
15.1 Introduction 317
15.2 The State-of-the-art of Biomedical Applications of Nano-Products 318
15.3 The Scientific Perspective on Nano-products for Biomedical Applications, Risks, and Regulations 322
15.4 Using RRI as a Methodological Pathway Toward Communication Between the Science System and the Law System 324
15.5 Final Considerations and New Propositions 340
Notes 341
References 342
16 Nanoethics and Nanotechnology 349
Iti Chauhan, Madhu Verma, and Mohd Yasir
16.1 Introduction 349
16.1.1 Types of Nanotechnology 349
16.1.2 Applications of Nanotechnology 349
16.2 Nanoethics 351
16.2.1 Regulatory Agencies 354
16.2.1.1 Nanotechnology and State Regulation (India) 355
16.2.2 Distributive Justice 356
16.2.2.1 Bridging the Gap 357
16.2.3 Nanoweapons 358
16.2.4 Ethics in Nanomedicine 358
16.2.4.1 Ethics in Research and Development 359
16.2.4.2 Health and Safety Issues 360
16.2.4.3 Toxicity Associated with Nanoparticulate System 361
16.2.5 Privacy and Confidentiality 361
16.2.6 Human Enhancement 362
16.2.7 Nanopollution 363
16.2.7.1 Health Issues 363
16.2.7.2 Measuring Nanomaterials’ Concentration in the Environment 364
16.2.7.3 Environmental Issues 365
16.2.7.4 Social Issues 365
16.2.7.5 Speculative Issue 366
16.2.8 Educational Issues 367
16.2.9 Biological Issues 367
16.3 Conclusion 368
References 368
17 Current Regulatory Framework in Nanotechnology and Medicine 373
Nitin Dubey and Nidhi Dubey
17.1 Introduction 373
17.1.1 Classification of Nanomaterials 374
17.1.2 Nanoparticles 374
17.2 Quality Attributes and Regulatory Concerns of Nanomaterials 375
17.2.1 Physicochemical Characterization 375
17.2.2 Nonclinical Studies for Nanomaterials 376
17.2.3 Clinical Studies for Nanomaterials 377
17.2.4 Identification of Hazardous Material 377
17.2.5 Exposure Risk to Humans and Environment During Nanomaterial Manufacturing, Storage, or Disposal 378
17.3 Quality Assessment of Nanomedicines 380
17.4 Current Regulatory Framework over Nanomaterials 381
17.4.1 USA 382
17.4.1.1 ANSI 387
17.4.1.2 ASTM 387
17.4.2 European Union 387
17.4.2.1 CEN 390
17.4.3 Taiwan 390
17.4.4 Iran 390
17.4.5 Canada 390
17.4.6 Australia 391
17.4.7 Japan 392
17.4.8 India 392
17.4.9 People’s Republic of China 393
17.4.10 Republic of Korea 394
17.4.11 Russia 394
17.4.12 WHO 394
17.4.13 OECD 394
17.4.14 ISO 396
17.4.15 VAMAS 397
17.5 Conclusion and Future Outlook 401
References 402
Index 407
