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Nanoparticles for Therapeutic Applications. Edition No. 1. Advances in Nanotechnology and Applications

  • Book
  • 592 Pages
  • July 2022
  • John Wiley and Sons Ltd
  • ID: 5633046
NANOPARTICLES FOR THERAPEUTIC APPLICATIONS

The main goal of this book is to provide information on theranostic applications of various nanomaterials for different diseases with self-explanatory illustrations and fundamental descriptions of a plethora of properties of molecular traits.

The author has written a fascinating book on research topics and fundamentals in the cross-disciplinary area of nanotechnology and bioscience in which she successfully fuses otherwise divergent research topics of this rapidly emerging area.

The book deals with the use of nanomaterials for combatting various diseases and disorders of the human body. The three chapters of the first part of this book deal with the areas in which nanotechnology has contributed to nanomedicine. In the second part, different disorders like cancer, neurodegenerative diseases, genetic diseases, infectious diseases, cardiovascular disorders, eye, dentistry, bone, and cartilage-affecting diseases are discussed. In the chapters related to a disease or disorder of a particular organ, a basic brief introduction to them is given as well.

Audience

The book will be read by researchers, scientists, and graduate students in biotechnology, nanotechnology, materials science, and nanomedicine/biomedicine.

Table of Contents

Foreword xxi

Preface xxiii

Part I: Nano-Flotillas Traversing in the Vein as Carriers to Deliver Theranostics 1

1 Diagnostic and Therapeutic Systems Using Nanomaterials 3

1.1 Introduction 3

1.2 Nanodiagnostic Agents 4

1.2.1 Bio-Barcode Assay (BCA) 5

1.2.2 Cantilever Beam 5

1.2.3 Carbon Dots/Carbon Quantum Dots 8

1.2.3.1 CD as Bioimaging Agent 9

1.2.3.2 CD as Sensor 10

1.2.4 Carbon Nanotubes (CNTs) 11

1.2.4.1 Diagnostic Equipment Using CNT 13

1.2.5 Dendrimers 26

1.2.5.1 Types of Dendrimers 27

1.2.5.2 Applications of Dendrimers 28

1.2.6 DNA 30

1.2.7 Nanocrystals/Quantum Dots (QDs) 33

1.2.7.1 Applications of Nanocrystals/Quantum Dots (QDs) 34

1.2.8 Nanoparticles as Diagnostic Tool 35

1.2.8.1 Inorganic/Metal Nanoparticles 35

1.2.8.2 Polymeric Nanoparticles (PNPs) 43

1.2.9 Nanorobotics 45

1.2.10 Nanoshells 47

1.2.11 Nanowires 48

1.2.12 Optical Tweezers 48

1.2.13 Serum Albumin 50

1.3 Summary 51

References 51

2 Nano Trojan Horses for Delivery of Peptides and Protein Drugs 57

Roopa Dharmatti

2.1 Introduction 57

2.2 Peptides 58

2.2.1 Cell-Penetrating Peptides 61

2.2.1.1 CPP and NP Surface Conjugation Mechanism 62

2.2.1.2 CPP-NP Conjugates in Cancer 64

2.2.1.3 CPP-NP Conjugates in Inflammation 65

2.2.1.4 CPP-NPs Conjugates in Central Nervous System Disorders 66

2.2.2 Antimicrobial Peptides (AMPs) 66

2.2.2.1 Nanomedicines for Antimicrobial Peptides Delivery 68

2.2.3 Peptide Toxins 70

2.2.3.1 Action Mechanism of Peptide Toxins 71

2.2.3.2 Therapeutic Applications of Peptide Toxins from Various Sources 71

2.2.4 Modifications of Natural Peptides for NP and Drug Design 77

2.3 Role of Nanoparticles in Peptide Drug Delivery 77

2.3.1 Vasoactive Intestinal Peptide (VIP) NPs for Diagnostics and for Controlled and Targeted Drug Delivery 79

2.3.1.1 NPs for VIP Drug Delivery 80

2.3.1.2 Structural Basis for Neuropeptide VIP-Targeted Drug Delivery Aided by Nanotechnology 82

2.4 Protein 85

2.4.1 Protein and Peptide Drug Conjugates 86

2.4.1.1 Protein-Drug Conjugates 86

2.4.1.2 Strategies for Chemical Conjugation 90

2.5 Role of Nanoparticles (NPs) in Protein Drug Delivery 96

2.5.1 Liposomes 96

2.5.2 Nanoparticles (NPs) Made from Polymer 97

2.5.3 Carbon Nanotubes (CNTs) 99

2.5.4 Other Metal Nanoparticles (NPs) 100

2.6 Summary 102

References 102

3 Biomimetic Nanomaterials as Smart Scaffolds for Tissue Regeneration 115

3.1 Introduction 115

3.1.1 Concept of Tissue Engineering (TE) 116

3.1.2 A Brief Look at the Type of Tissue-Specific Stem Cells Being Engineered for Tissue Regeneration 117

3.1.3 Growth Factor 119

3.2 Scaffold 119

3.2.1 Basic Requirements for Scaffold 120

3.2.1.1 Biocompatibility of Scaffold Material 120

3.2.1.2 Biodegradability of Scaffold Material 121

3.2.1.3 Mechanical Properties of Scaffold Material 121

3.2.1.4 Porosity in Scaffold Architecture 121

3.2.1.5 Surface Chemistry of Scaffold 121

3.2.2 Biological Scaffold Fabrication Techniques 122

3.2.2.1 Conventional Fabrication Techniques 122

3.2.2.2 Rapid Prototyping (RP) Technique or Solid Free-From Fabrication Technique 125

3.2.2.3 Decellularization 128

3.2.2.4 Tissue Vascularization and Integration 129

3.2.2.5 3D Bioprinting or Cell Printing 129

3.2.2.6 Crosslinking of Hydrogel 132

3.3 Biomaterials for the Fabrication of Scaffold 132

3.3.1 Natural Biomaterials and Extracellular Matrix Material (ECM) Used for Scaffolding 132

3.3.1.1 Collagen 133

3.3.1.2 Fibrin 134

3.3.1.3 Gelatin 136

3.3.1.4 Silk Fiber 137

3.3.1.5 Proteoglycan (PG) 137

3.3.1.6 Hyaluronan or Hyaluronic Acid (HA) 138

3.3.1.7 Chitosan 138

3.3.1.8 Alginate 139

3.3.1.9 Silica 140

3.3.1.10 Poly(Ethylene Glycol) (PEG) 140

3.3.2 Synthetic Biodegradable Polymer Biomaterials Used for Scaffolding 141

3.3.2.1 Poly(L-lactic Acid) (PLA) Scaffold 142

3.3.2.2 Polyglycolide (PGA) Scaffold 142

3.3.2.3 Poly(Lactic-co-Glycolic Acid) (PLGA) Scaffold 142

3.3.2.4 Polycaprolactone (PCL) Scaffold 143

3.3.2.5 Hydrogel 143

3.3.3 Ceramics 143

3.3.4 Functionality of Types of Scaffolds 144

3.3.4.1 Injectable Material for Scaffolds or ‘Injectabone’ 144

3.3.4.2 Scaffold as Delivery System for Growth Factor and Drugs 144

3.3.4.3 Supercritical Carbon Dioxide Processing of Polymers 145

3.3.4.4 Customized Scaffold via 3D Printing 145

3.3.4.5 Plasma Modification of Scaffold Surfaces 146

3.4 Nanomaterials for Versatile Scaffolds 146

3.4.1 Carbon-Based Nanoparticle Carbon Nanotubes as Versatile Scaffolds 148

3.4.2 Metal Nanoparticles 152

3.4.2.1 Tantalum (Ta) 153

3.4.2.2 Magnesium and Its Alloys 153

3.4.2.3 Titanium and Its Alloys 154

3.4.2.4 Silver Nanoparticles (AgNPs) 154

3.4.2.5 Aluminum Nanoparticles (AlNPs) 155

3.4.2.6 Gold Nanoparticles (AuNPs) 156

3.4.2.7 Copper Nanoparticles (CuNPs) 157

3.4.2.8 Iron (Fe), Iron Oxide and Its Conjugate Nanoparticles 158

3.4.2.9 Nickel Nanoparticles (NiNPs) 159

3.4.2.10 Zirconium Nanoparticles (ZrNPs) 160

3.4.3 Polymeric Nanoparticles and Nanofibers 160

3.4.4 Lipid-Based Nanoparticles 161

3.4.4.1 Liposomes 162

3.4.5 Ceramic Nanoparticles (CNPs) 163

3.4.5.1 Bioactive Ceramic Nanoparticles 164

3.4.5.2 Bioinert Ceramic Nanoparticles 164

3.4.5.3 Bioresorbable Ceramic Nanoparticles 164

3.4.6 Natural Extracellular Matrix (ECM) 165

3.5 Application of Scaffold for Various Tissue Regeneration and Incorporation of Nanomaterials 165

3.5.1 Scaffold for Bone Tissue Regeneration 166

3.5.2 Scaffold for Cartilage Tissue Regeneration 170

3.5.3 Scaffold for Cardiovascular Tissue Regeneration 172

3.5.4 Scaffold for Liver Tissue Regeneration 173

3.5.5 Scaffold for Muscle Tissues Regeneration 175

3.5.6 Scaffold for Nerve Tissue Regeneration 176

3.5.7 Scaffold for Skin Tissue Regeneration 180

3.5.8 Scaffold for Tendon and Ligament Tissue Regeneration 183

3.6 Considerations for Manufacturing a Scaffold at Commercial Level 186

3.7 Conclusion 187

References 187

Part II: The Cardinal Role of Biomedical Nanotechnology 209

4 Nanodiagnostics and Nanotherapeutics: A Powerful Tool for Ablation of Cancer 211

4.1 Introduction 211

4.2 Molecular Diagnostics 212

4.2.1 Radioimmunoassay (RIA) 215

4.2.2 Enzyme-Linked Immunosorbent Assay (ELISA) 215

4.2.3 SDS-Page and Western Blot 216

4.2.4 Immunoprecipitation (IP) 217

4.2.5 Immunofluorescence 218

4.2.6 Immunoelectron Microscopy 218

4.2.7 Polymerase Chain Reaction (PCR) 218

4.3 Radiological Diagnostics for Cancer 219

4.3.1 Computerized Tomography (CT) Scan 219

4.3.2 Magnetic Resonance Imaging (MRI) 219

4.3.3 Positron Emission Tomography (PET) 220

4.4 Biopsy 222

4.5 Nanodiagnostics for Cancer 223

4.5.1 Brain Cancer 224

4.5.1.1 Brain Cancer and Nanotechnology 226

4.5.2 Breast Cancer 228

4.5.2.1 Breast Cancer and Nanodiagnostic 230

4.5.3 Colon/Colorectal Cancer 230

4.5.3.1 Colon/Colorectal Cancer and Nanodiagnostic 231

4.5.4 Liver Cancer or Hepatocellular Carcinoma (HCC) 233

4.5.4.1 Liver Cancer and Nanotechnology 234

4.5.5 Lung Cancer 239

4.5.5.1 Lung Cancer and Nanotechnology 240

4.5.6 Melanoma and Skin Cancer 242

4.5.6.1 Melanoma and Nanotechnology 244

4.5.7 Oral Cancer 246

4.5.7.1 Oral Cancer and Nanotechnology 247

4.5.8 Ovarian Cancer 248

4.5.8.1 Ovarian Cancer and Nanotechnology 249

4.5.9 Pancreatic Cancer 251

4.5.9.1 Pancreatic Cancer and Nanotechnology 252

4.5.10 Prostate Cancer 255

4.5.10.1 Prostate Cancer and Nanotechnology 257

4.5.11 Renal Cancer/Kidney Cancer 259

4.5.11.1 Renal Cancer and Nanotechnology 261

4.5.12 Urinary Bladder Cancer 261

4.5.12.1 Urinary Bladder Cancer and Nanotechnology 262

4.6 Summary 264

References 265

5 Genetic Diseases and Nanotechnology-Based Theranostics 277

5.1 Introduction 277

5.2 Nanotechnologies and Microchips in Genetic Diseases 279

5.3 Nanotechnology and Gene Therapy for Genetic Disease 279

5.3.1 Diabetic Retinopathy (DR) 281

5.3.2 Some Diseases Successfully Treated with Nanotechnology + Gene Therapy 282

5.4 Gene Silencing Therapy 284

5.5 Ribonucleic Acid (RNA) Therapy and Nanotechnology 286

5.6 Nanoparticles-Based Therapies for Various Chromosomal Disorders 287

5.6.1 Down Syndrome 287

5.6.1.1 Mosaic Down Syndrome 287

5.6.1.2 Translocation Down Syndrome 288

5.6.1.3 Klinefelter Syndrome (47,XXY) 288

5.6.1.4 Turner Syndrome 288

5.6.1.5 Williams Syndrome 288

5.6.1.6 Cri du Chat Syndrome 289

5.6.2 Single-Gene Disorder 289

5.6.2.1 Niemann-Pick Type C1 Disease (NPC1) 289

5.6.2.2 Cystic Fibrosis 290

5.6.2.3 Galactosemia 291

5.6.2.4 Severe Combined Immunodeficiency (SCID) 292

5.6.2.5 Sickle Cell Disease (SCD) 292

5.6.2.6 Huntington’s Disease (HD) 293

5.6.2.7 Tay-Sachs Disease 294

5.6.3 Multifactorial Disorders 295

5.6.3.1 Thalassemia 295

5.6.3.2 Mitochondrial Disease 296

5.7 Summary 299

References 299

6 The Role of Biomedical Nanotechnology in CNS and Neurological Disorders 303

6.1 Introduction 303

6.2 Parkinson’s Disease 304

6.2.1 Nanotheranostic for Parkinson’s Disease (PD) 306

6.3 Alzheimer’s Disease 309

6.3.1 Nanotheranostic for Alzheimer’s Disease 312

6.4 Epilepsy/Seizure Disorder 316

6.4.1 Nanotheranostic for Epilepsy 318

6.5 Schizophrenia 319

6.5.1 Nanotheranostic for Schizophrenia 320

6.6 Summary 323

References 324

7 Nanotechnology-Based Theranostics for Fighting Infectious Diseases 329

7.1 Introduction 329

7.2 Diseases Caused by Prions 333

7.2.1 Nanotheranostic for Diseases Caused by Prions 334

7.3 Diseases Caused by Virus 336

7.3.1 HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome) and Nanotheranostic 339

7.3.2 Hepatitis C Virus and Nanotheranostic 341

7.3.3 Dengue Virus and Nanotheranostic 344

7.3.4 Polio Virus and Nanotheranostic 347

7.3.5 Meningitis-Causing Virus and Nanotheranostic 349

7.3.6 Herpes-Causing Virus and Nanotheranostic 351

7.3.7 Influenza (Flu)-Causing Virus and Nanotheranostic 354

7.3.8 COVID-19 (Coronavirus) Nanotheranostic 357

7.4 Diseases Caused by Bacteria 362

7.4.1 Nanotheranostics for Diseases Caused by Bacteria 376

7.4.1.1 Antibacterial Nanoparticles, Nanoantibiotics and Nanotechnology 376

7.4.1.2 Nano-Strategies to Fight Multidrug-Resistant (MDR) Bacteria 376

7.4.1.3 Theranostics to Combat Biofilms of Bacteria 379

7.4.1.4 Theranostics for Bloodstream Infection 381

7.4.1.5 Nanoparticles for Drug Delivery 381

7.4.1.6 Modulation of Immune Response by Nanoparticles for Efficient Vaccination 382

7.5 Diseases Caused by Fungi 382

7.5.1 Nanotheranostic for Diseases Caused by Fungi 385

7.5.1.1 Nanotechnology for Cutaneous Fungal Infection Therapy 385

7.5.1.2 Nanotechnology for Invasive Mycoses Therapy 386

7.5.1.3 Nanotechnology for Ocular Mycoses Therapy 388

7.6 Diseases Caused by Parasitic Protozoa 389

7.6.1 Nanotheranostics for Diseases Caused by Parasitic Protozoa 393

7.6.1.1 Leishmaniasis, Chagas Disease and African Trypanosomiasis 394

7.6.1.2 Malaria 395

7.6.1.3 Amebiasis 396

7.6.1.4 Giardiasis 396

7.7 Diseases Caused by Helminths 397

7.7.1 Nanotheranostic for Diseases Caused by Parasitic Helminths 399

7.7.1.1 Nanotherapeutics and Nematodes (Roundworms) 399

7.7.1.2 Nanotherapeutics and Trematodes (Flatworms) 401

7.7.1.3 Nanotherapeutics and Cestodes (Tapeworms) 402

7.8 Summary 403

References 403

8 Nanotheranostics for Cardiovascular Diseases 419

8.1 Introduction 419

8.1.1 The Human Heart 419

8.1.2 Blood Vessels 419

8.1.3 Heart or Cardiovascular Diseases 421

8.1.4 Diseases of the Blood Vessels 423

8.1.5 Diagnostics and Therapeutics of Cardiovascular Disease 425

8.2 Nanotheranostics for Cardiovascular Diseases 426

8.2.1 Nanodiagnostics for Cardiovascular Disease 427

8.2.2 Nanotherapeutics for Cardiovascular Disease 429

8.2.2.1 Liposome NP for Cardiovascular Therapy 430

8.2.2.2 Polymeric Nanoparticles for Cardiovascular Therapy 431

8.2.2.3 Micelle NP for Cardiovascular Therapy 432

8.2.2.4 Dendrimers for Cardiovascular Therapy 434

8.2.2.5 Gel Nanoparticles for Cardiovascular Therapy 435

8.2.2.6 Metal Nanoparticles for Cardiovascular Therapy 435

8.2.2.7 Nanocoated Stents for Coronary Artery Bypass Graft (CABG), Percutaneous Transluminal Coronary Angioplasty (PTCA) and Percutaneous Coronary Intervention (PCI) 436

8.2.2.8 Nano Patch and Scaffold for Cardiovascular Disease 436

8.2.2.9 Suitability of Carbon Nanotubes for Cardiovascular Therapy 438

8.3 Summary 439

References 440

9 Role of Nanotechnology in Combatting Disease and Disorders of Ophthalmology 445

9.1 Introduction 445

9.2 Structure and Anatomy of the Human Eye 445

9.3 Eye Diseases and Disorders 449

9.3.1 Diseases and Disorders of Accessory Structures 449

9.3.1.1 Dry Eye 449

9.3.1.2 Conjunctivitis 450

9.3.1.3 Blepharitis/Blepharoptosis (Ptosis) 450

9.3.1.4 Hordeolum (Stye) 450

9.3.1.5 Chalazion (Meibomian Cyst) 451

9.3.1.6 Entropion 451

9.3.1.7 Ectropion 451

9.3.2 Diseases and Disorders of Fibrous Tunic 451

9.3.2.1 Keratoconus 451

9.3.2.2 Refractive Errors 452

9.3.3 Diseases and Disorders of Vascular Tunic 453

9.3.3.1 Uveitis 453

9.3.4 Diseases and Disorders of Nervous Tunic 454

9.3.4.1 Color Blindness 454

9.3.4.2 Retinal Detachment 454

9.3.4.3 Diabetic Retinopathy (DR) 456

9.3.4.4 Age-Related Macular Degeneration (AMD) 457

9.3.5 Diseases and Disorders of Interior Eyeball 457

9.3.5.1 Glaucoma 457

9.3.5.2 Cataract 459

9.3.5.3 Floater 461

9.3.6 Diseases and Disorders of Cornea and Uveal Tract 461

9.3.6.1 Pterygium 461

9.3.6.2 Keratitis 462

9.3.6.3 Scleritis 462

9.3.6.4 Iritis 463

9.3.7 Muscular Disorders 463

9.3.7.1 Nystagmus 463

9.3.7.2 Strabismus (Crossed Eyes) 463

9.4 Blindness 463

9.4.1 Trachoma 464

9.5 Nanotherapy for Ocular Diseases and Disorders 464

9.5.1 Nanotechnology for Regenerative Ophthalmology 465

9.5.1.1 Nanoscaffolds for Retinal Tissue Regeneration 466

9.5.1.2 Nanoscaffolds for Corneal Tissue Regeneration 468

9.5.2 Nanomaterials as Gene Delivery Devices to Reprogram Cells for Ocular Regeneration 470

9.5.2.1 Lipoplexes: Liposome-Protamine-DNA (LPD) Nanocomplexes 471

9.5.2.2 Polyplexes 471

9.5.2.3 Mesoporous Nanoparticles 472

9.5.2.4 Organic-Inorganic Hybrid Nanocrystals 472

9.5.2.5 NanoScript Nanoparticle 472

9.5.2.6 Self-Assembling DNA and Magnetic Nanoparticles 473

9.5.3 Nanomaterials as Immunomodulator in Ocular Regeneration 473

9.6 Glaucoma: Potential Implications of Nanotechnology and Nanomedicine 475

9.6.1 Drug Delivery System for Arresting Glaucoma 475

9.7 Cataract: Potential Implications of Nanotechnology and Nanomedicine 480

9.7.1 Nanoscaffolds for Lens Regeneration (Cataract) 480

9.7.2 Nanofiber-Based Hydrogel 481

9.8 Uveitis (Eye Inflammation) Therapy by Nanozyme (Superoxide Dismutase 1) 482

9.9 Contact Lenses for Ocular Theranostic 482

9.10 Nanodiagnostic for Ocular Diseases and Disorders 483

9.11 Summary and Future Perspective 484

References 485

10 Use of Nanotechnology in Dentistry 493

10.1 Introduction 493

10.1.1 Structure of Human Teeth 493

10.1.2 Types of Human Teeth 494

10.2 Diseases and Disorders of Teeth 495

10.2.1 Plaque Formation 495

10.2.2 Caries (Cavities) 496

10.2.3 Periodontal Disease 496

10.2.3.1 Periodontitis 497

10.2.3.2 Gingivitis 497

10.2.4 Trench Mouth 497

10.2.5 Thrush 497

10.2.6 Periapical Abscess (Dentoalveolar Abscess) 498

10.2.7 Malocclusion 498

10.2.8 Dry Mouth 498

10.2.9 Herpetic Gingivostomatitis 498

10.2.10 Mumps 499

10.2.11 Mouth Ulcer 499

10.2.12 Stained Teeth 500

10.2.13 Hyperdontia (Extra Teeth) 500

10.3 Nanotheranostics Used in Dentistry 500

10.3.1 Nanotechnology for Diagnosis 501

10.3.1.1 Nanocantilevers for Diagnostics 503

10.3.1.2 Nanopores/Porous Nanoparticles for Diagnostics 503

10.3.1.3 Nanotubes for Diagnostics 503

10.3.1.4 Quantum Dots (QD) for Diagnostics 503

10.3.1.5 Nanoelectromechanical Systems (NEMS) for Diagnostics 504

10.3.1.6 Lab-on-a-Chip or Biochips and Salivary Biomarkers for Diagnostics 504

10.3.1.7 Oral Fluid Nanosensor Test (OFNASET) for Diagnostics 505

10.3.1.8 Nanorobots or Dentifrobots for Diagnostics 506

10.3.1.9 Digital Dental Imaging for Diagnostics 507

10.3.2 Nanomaterials Used in Dental Therapeutics 507

10.3.2.1 Organic Nanomaterials for Therapeutics 507

10.3.2.2 Inorganic Nanomaterials for Therapeutics 508

10.3.2.3 Nanocomposites for Therapeutics 509

10.3.2.4 Carbon-Based Nanomaterials for Therapeutics 511

10.3.2.5 Nonsolution (Nano Adhesive) for Therapeutics 511

10.3.2.6 Nano Light-Curing Glass Ionomer Restorative 511

10.3.2.7 Nanoneedles 512

10.3.3 Role of Nanotechnology in Dental Tissue Engineering 512

10.3.3.1 Nanotechnology in Bone Grafting/Regeneration and Oral Maxillofacial Surgery 514

10.3.3.2 Nanotechnology for Dental Pulp Regeneration 514

10.3.3.3 Nanostructures and Enamel Tissues Engineering/Restoration 515

10.3.3.4 Nanotechnology and Nerve Regeneration 515

10.3.4 Bio-Nanofunctionalized Surface of Dental Implants 517

10.3.4.1 Prosthodontics and Nanotechnology 518

10.3.5 Nanomaterials for Periodontal Drug Delivery 520

10.3.6 Endodontics 522

10.3.7 Nanoanesthesia 524

10.3.8 Nanotechnology and Dental Disease Prevention 524

10.3.8.1 Nano Toothbrush 525

10.3.8.2 Nano-Modified Toothpaste and Mouthwash 525

10.3.8.3 Nanomaterials for Prevention of Caries 526

10.3.8.4 Nanomaterials for Prevention of Periodontal Disease 530

10.3.9 Antimicrobial Photodynamic Therapy (APDT) 531

10.4 Conclusion 534

References 535

Index 545

Authors

Madhuri Sharon