Nanomedicine in Brain Diseases (eBook)

Preface 5
Acknowledgments 6
Contents 7
Chapter 1: Introduction: Nanomedicine in the Brain 13
1.1 Introduction 13
1.2 Application of Nanomedicine 15
1.2.1 Magnetic-Based Nanomaterials 17
1.2.2 Carbon-Based Nanomaterials 17
1.2.3 Silicon-Based Nanomaterials 18
1.2.4 Lipid-Based Nanomaterials 19
1.2.5 Rare-Earth Elements-Based Nanomaterials 19
1.2.6 Quantum Dots 20
1.2.7 Metallic Organic Framework Compounds 20
1.2.8 Others 21
1.3 Overview of Neuropsychiatric Disease 22
1.3.1 Neurological Disease 23
1.3.1.1 AD 23
1.3.1.2 PD 24
1.3.1.3 Stroke 26
1.3.1.4 MS 28
1.3.1.5 Glioblastoma 28
1.3.2 Psychiatric Disease 29
1.3.2.1 Depression 30
1.3.2.2 Schizophrenia 30
1.3.2.3 Other Psychiatric Disease 31
1.4 Conclusion and Perspective 31
References 33
Chapter 2: The Strategies of Nanomaterials for Traversing Blood-Brain Barrier 41
2.1 Introduction 42
2.2 BBB Structure and Passage Mechanism 43
2.3 Different Strategies for Targeting of Drugs to the Brain 46
2.4 Convection-Enhanced Delivery (CED) 46
2.5 Intranasal Delivery to Bypass BBB 47
2.6 Employment of NPs for Drug Delivery into the Brain 48
2.7 Aspects Affecting the Entry of NPs over the BBB 49
2.8 Different Types of Nanoparticles Employed to Cross BBB 51
2.8.1 Liposomes 51
2.8.2 Lipid-Based NPs 53
2.8.3 Polymer-Based Nanocarriers Across the BBB 53
2.9 Employment of Different siRNA-Based Deliveries 55
2.9.1 Exosome-Based Delivery 56
2.9.2 Employment of Cell-Penetrating Peptides (CPPs) 57
2.9.3 Other Types of NPs 57
2.10 Mechanism of Nanoparticle Route to BBB 59
2.11 Neurotoxicity of the Nanoparticles 61
2.12 A Future Point of View 62
2.13 Conclusion 62
References 63
Chapter 3: The Strategies of Nanomaterials for Drug Delivery and Release 70
3.1 Introduction 70
3.2 Nanopreparations for Brain Diseases 72
3.2.1 Construction of Nanocarriers 72
3.2.2 Types of Nanopreparations for Brain Disease 73
3.2.2.1 Nanoparticles 74
3.2.2.2 Dendrimer 75
3.2.2.3 Micelle 75
3.2.2.4 Liposome 76
3.2.2.5 Others 76
3.3 Advances in Drug Delivery and Release Approaches for Brain Diseases 77
3.3.1 Controlled Nano Drug Delivery Systems 77
3.3.2 Targeted Nano Drug Delivery Systems 77
3.3.2.1 Passive Targeting 77
3.3.2.2 Active Targeting 78
3.3.2.2.1 Receptors-Related Endocytosis 79
3.3.2.2.2 Transporters-Mediated Active Targeting 80
3.3.2.2.3 Cell-Penetrating Peptides-Mediated Active Targeting 81
3.3.2.2.4 Adsorptive-Mediated Active Targeting 81
3.3.2.3 Magnetic Targeting 81
3.3.2.4 Dual Targeting 82
3.3.3 Smart Response Nano Drug Delivery and Release Systems 83
3.3.3.1 PH-Sensitive Nanopreparations 84
3.3.3.2 ROS-Sensitive Nanopreparations 84
3.3.3.3 Temperature-Sensitive Nanopreparations 85
3.3.3.4 Others 86
3.3.4 Intranasal Drug Delivery Systems 86
3.4 Conclusion 87
References 87
Chapter 4: The Strategies of Nanomaterials for Therapy 94
4.1 Introduction 94
4.2 Nanomaterials for Brain Tumor Treatment 95
4.2.1 Nanomaterial-Based Chemotherapy 95
4.2.2 Nanomaterial-Based Gene Therapy 96
4.2.3 Nanomaterial-Based Thermotherapy 98
4.2.4 Nanomaterial-Based Photodynamic Therapy 99
4.2.5 Nanomaterial-Based Immunotherapy 100
4.3 Nanomaterials for Alzheimer´s Disease Treatment 100
4.3.1 Nanomaterials for Drug Delivery 101
4.3.1.1 Cholinesterase Inhibitors and Acetylcholine Nanocarriers 101
4.3.1.2 Hormone Nanocarrier 102
4.3.1.3 Curcuminoids Nanocarrier 102
4.3.1.4 Polyphenol Nanocarrier 102
4.3.2 Nanomaterial-Based Metal Chelation Strategy 102
4.3.2.1 Iron Chelators 103
4.3.2.2 Copper Chelators 103
4.3.2.3 Zinc Chelators 103
4.3.3 Nanomaterials for Antioxidant 104
4.3.3.1 Fullerenes 104
4.3.3.2 Nanoceria 104
4.3.4 Nanomaterial-Based Gene Therapy 105
4.3.5 Nanomaterial-Based Immunotherapy 106
4.4 Nanomaterials for Parkinson´s Disease Treatment 107
4.4.1 Nanomaterials for Dopamine Replacement 108
4.4.2 Nanomaterials for Dopaminergic Agonist Delivery 108
4.4.3 Nanomaterials for Growth Factor and Peptides Delivery 110
4.4.3.1 Growth Factor 110
4.4.3.2 Peptides 111
4.4.4 Nanomaterial-Based Gene Therapy 111
4.5 Nanomaterials for Stroke Treatment 112
4.5.1 Nanomaterials for Thrombolysis 113
4.5.1.1 Tissue Plasminogen Activator (tPA) Delivery 113
4.5.1.2 Heparin Delivery 114
4.5.2 Nanomaterials for Neuroprotection 114
4.5.2.1 Antioxidant and Anti-inflammatory Agents Delivery 114
4.5.2.2 Antioxidant Enzymes Delivery 114
4.5.2.3 Nanomaterial-Based Stem Cell Therapy 116
4.5.3 Nanomaterial-Based Gene Therapy 116
4.6 Conclusion 117
References 117
Chapter 5: Overcoming the Physiopathologic Barriers: Nanoprobes-Mediated Intracranial Glioma Imaging 126
5.1 Introduction 127
5.2 Critical Biological Challenges Facing Intracranial Glioma 128
5.3 Strategies for Bypassing and Crossing BBB 129
5.4 Advantages of Nanomaterials for Glioma Imaging 130
5.5 Applications of Nanoprobes for Intracranial Glioma Imaging 131
5.5.1 Magnetic Resonance Imaging 132
5.5.2 Photoacoustic Imaging 136
5.5.3 Fluorescence Imaging 138
5.5.4 Multimodal Imaging 140
5.5.5 Intraoperative Glioma Margin Delineation 143
5.6 Challenges and Perspectives 145
References 146
Chapter 6: The Advances of Nanozyme in Brain Disease 150
6.1 Introduction 150
6.2 ROS-Mediated Oxidative Stress and Its Role in Neurological Diseases 152
6.3 Nanozymes with Antioxidant Activity 155
6.3.1 Nanozymes with SOD-Like Activity 156
6.3.1.1 Nanoceria with SOD-Like Activity 156
6.3.1.2 Fullerene and Its Derivatives with SOD-Like Activity 158
6.3.1.3 Carbon Clusters with SOD-Like Activity 159
6.3.1.4 Platinum Nanoparticles with SOD-Like Activity 161
6.3.2 Nanozymes with Catalase-Like Activity 161
6.3.2.1 Nanoceria with Catalase-Like Activity 162
6.3.2.2 Iron Oxide Nanoparticles with Catalase-Like Activity 164
6.3.2.3 Co3O4 Nanozymes with Catalase-Like Activity 165
6.3.2.4 Platinum Nanoparticles with Catalase-Like Activity 165
6.3.3 Nanozymes with Multiple Antioxidant Enzyme-Like Activities 166
6.3.3.1 Mn3O4 Nanozyme 167
6.4 Nanozymes Used for the Treatment of Neurological Diseases 169
6.4.1 Application of Nanozymes in Neuroprotection 169
6.4.2 Application of Nanozymes in Alzheimer´s Disease 174
6.4.3 Application of Nanozymes in Cerebral Ischemia 179
6.4.4 Application of Nanozymes in Parkinson´s Disease 181
6.4.5 Application of Nanozymes in Multiple Sclerosis 182
6.5 Challenges and Perspectives 182
References 184
Chapter 7: The Advances of Biomacromolecule-based Nanomedicine in Brain Disease 191
7.1 Introduction 191
7.2 Key Constraint Factors for Biomacromolecule Delivery into the Brain 192
7.2.1 Blood-Brain Barrier (BBB) 192
7.2.2 Blood Cerebrospinal Fluid Barrier (BCFB) and Blood Tumor Barrier (BTB) 193
7.2.3 Drug Diffusion in the Brain 193
7.3 Strategies for Biomacromolecular Nanomedicine Delivery into the Brain 194
7.3.1 Direct Injections 194
7.3.2 Convection-Enhanced Delivery (CED) 195
7.3.3 Intranasal Administration 195
7.3.4 Oral Administration 196
7.3.5 BBB Disruption 196
7.3.6 Ultrasound and Microbubble with Nanoparticles 197
7.3.7 Targeted Brain Delivery 197
7.4 Preclinical and Clinical Advances of Biomacromolecular Nanomedicines for Brain Disease Treatment 198
7.4.1 Protein-Based Nanomedicine 198
7.4.2 Enzyme-Based Nanomedicine 199
7.4.3 Peptide-Based Nanomedicine 202
7.4.4 Antibody-Based Nanomedicine 203
7.4.5 Nucleic Acid-Based Nanomedicine 206
7.4.5.1 Current Status of Nucleic Acid-Based Therapeutics 206
7.4.5.2 siRNA 207
7.4.5.3 ASO 208
7.4.5.4 DNA and mRNA 208
7.5 Concerns over Biomacromolecular Nanomedicines 209
7.6 Conclusion and Prospective 210
References 210
Chapter 8: Carbon-Based Nanomedicine 219
8.1 Introduction 219
8.2 Application 220
8.2.1 Drug Carrier 220
8.2.2 Gene Carrier 221
8.2.3 Photodynamic Therapy (PDT) and Photothermal Therapy (PTT) 223
8.2.4 Imaging Agent 224
8.3 Pharmacodynamics and Metabolism 227
8.3.1 Delivery to the Brain 227
8.3.2 Toxicological Characteristics 228
8.3.3 Drug Release 229
8.4 Diagnosis and Treatment 231
8.4.1 Neurodegenerative Disease 231
8.4.2 Tumor 231
8.4.3 Acute Hyperglycemia 233
8.5 Biodistribution of Carbon Nanomaterials 234
8.5.1 Brain Distribution 234
8.5.2 Body Distribution 236
8.6 Summary 238
References 238
Chapter 9: Polymeric Nanomedicine 242
9.1 Introduction: Polymeric Nanomedicine and Polymeric Nanoparticles 242
9.2 Various Polymeric Nanoparticles 244
9.2.1 Polymeric Micelles 244
9.2.2 Core-Shell Nanocarriers 246
9.2.3 Nanospheres 248
9.2.3.1 Chitosan 248
9.2.3.2 PLGA Nanoparticles 250
9.2.3.3 PBCA Nanoparticles 251
9.2.4 Nanocapsules 251
9.2.5 Dendrimers 252
9.2.6 Nanogels 254
9.3 The Application of Polymeric Nanomedicine in Brain Disease 255
9.3.1 Brain Cancers 255
9.3.2 Alzheimer´s Disease 259
9.3.3 Cerebral Amyloid Angiopathy (CAA) 264
9.3.4 Parkinson´s Disease (PD) 265
9.3.5 Stroke 268
9.3.6 Multiple Sclerosis 271
References 271
Chapter 10: Magnetic Nanomedicine 277
10.1 Nanomaterials 278
10.2 Magnetic Nanoparticles 279
10.3 Synthesis Method of MNPs 283
10.3.1 Ball Milling Method 284
10.3.2 Chemical Methods 286
10.3.3 Coprecipitation 286
10.3.4 Thermal Decomposition 287
10.3.5 Hydrothermal Synthesis 288
10.4 Magnetic Nanoparticles as Hyperthermia Agent 291
10.4.1 Parameters Affecting the Heating Efficiency 292
10.5 Magnetic Nanoparticles for Drug Delivery 297
10.5.1 Drug Delivery Mechanism 298
10.5.2 MNPs in Drug Delivery 300
10.6 Magnetic Resonance Imaging (MRI) 303
10.6.1 MRI Contract Agents 304
10.6.2 The Longitudinal Relaxation (T1) Agents 305
10.6.3 The Transverse Relaxation (T2) Agents 307
10.7 Conclusion and Prospective 308
References 310