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Summary
Summary
This first comprehensive yet concise overview of all important classes of biological and pharmaceutical nanomaterials presents in one volume the different kinds of natural biological compounds that form nanomaterials or that may be used to purposefully create them. This unique single source of information brings together the many articles published in specialized journals, which often remain unseen by members of other, related disciplines. Covering pharmaceutical, nucleic acid, peptide and DNA-Chitosan nanoparticles, the book focuses on those innovative materials and technologies needed for the continued growth of medicine, healthcare, pharmaceuticals and human wellness.
For chemists, biochemists, cell biologists, materials scientists, biologists, and those working in the pharmaceutical and chemical industries.
Author Notes
Challa Kumar is currently the Group Leader of Nanofabrication at the Center for Advanced Microstructures and Devices (CAMD), Baton Rouge, USA. His research interests are in developing novel synthetic methods for functional nanomaterials and innovative therapeutic, diagnostic and sensory tools based on nanotechnology. Prior to eight years of industrial R&D with ICI and United Breweries, he researched at the Max Planck Institutes for Biochemistry in Munich and for Carbon Research in Mülheim, both Germany. He obtained his Ph.D. in synthetic organic chemistry from Sri Sathya Sai Institute of Higher Learning, Prashanti Nilayam, India.
Table of Contents
Preface | p. XIV |
List of Contributors | p. XVII |
I DNA-based Nanomaterials | p. 1 |
1 Self-assembled DNA Nanotubes | p. 3 |
1.1 Introduction | p. 3 |
1.2 DNA Nanotubes Self-assembled from DX Tiles | p. 4 |
1.3 3DAE-E DX Tile Nanotubes | p. 5 |
1.4 DAE-O DX Tile Nanotubes | p. 9 |
1.5 TX Tile Nanotubes | p. 11 |
1.6 4 x 4 Tile Nanotubes | p. 14 |
1.7 6HB Tile Nanotubes | p. 16 |
1.8 Applications | p. 18 |
1.9 Summary and Perspectives | p. 19 |
References | p. 20 |
2 Nucleic Acid Nanoparticles | p. 23 |
2.1 Introduction | p. 23 |
2.2 The Chemical and Physical Properties of Therapeutic DNA | p. 25 |
2.3 Preparation of Nucleic Acid Nanoparticles: Synthesis and Characterization | p. 27 |
2.3.1 Rationale | p. 27 |
2.3.2 Synthesis, Characterization and Optimization of Surfactants | p. 31 |
2.3.3 Organization of the Surfactant-DNA Complexes | p. 35 |
2.3.4 Quantification of the Stability of Surfactant-DNA Complexes | p. 35 |
2.4 DNA Functionalization for Cell Recognition and Internalization | p. 37 |
2.4.1 Strategies for Functionalization | p. 37 |
2.4.2 Intercalation | p. 38 |
2.4.3 Triple Helix Formation with Oligodeoxyribonucleotides | p. 39 |
2.4.4 Peptide Nucleic Acids (PNAs) | p. 41 |
2.4.5 Interactions of DNA with Fusion Proteins | p. 42 |
2.4.6 Agents that Bind to the Minor Groove | p. 43 |
2.5 DNA Nanoparticles: Sophistication for Cell Recognition and Internalization | p. 43 |
2.5.1 Preparation of DNA Nanoparticles Enveloped with a Protective Coat and Cell Internalization Elements | p. 43 |
2.5.2 Biomedical Application: Cell Targeting and Internalization Properties of Folate-PEG-coated Nanoparticles | p. 46 |
2.6 Concluding Remarks | p. 46 |
References | p. 47 |
3 Lipoplexes | p. 51 |
3.1 Introduction | p. 51 |
3.2 DNA Lipoplexes | p. 51 |
3.2.1 Composition | p. 51 |
3.2.2 Nanostructure and Microstructure | p. 52 |
3.2.2.1 Equilibrium Morphology | p. 52 |
3.2.2.2 Nonequilibrium Morphology | p. 55 |
3.2.2.3 Lipoplex Size | p. 57 |
3.2.3 Lipofection Efficiency | p. 57 |
3.2.3.1 In Vitro | p. 57 |
3.2.3.2 In Vivo | p. 59 |
3.3 ODN Lipoplexes | p. 60 |
3.4 siRNA Lipoplexes | p. 62 |
Acknowledgments | p. 62 |
References | p. 62 |
4 DNA-Chitosan Nanoparticles for Gene Therapy: Current Knowledge and Future Trends | p. 68 |
4.1 Introduction | p. 68 |
4.2 Chitosan as a Carrier for Gene Therapy | p. 69 |
4.2.1 Chitosan Chemistry | p. 69 |
4.2.2 General Strategies for Chitosan Modification | p. 71 |
4.2.3 Chitosan-DNA interactions: Transfection Efficacy of Unmodified Chitosan | p. 71 |
4.3 Modified Chitosans: Strategies to Improve the Transfection Efficacy | p. 79 |
4.3.1 The Effects of Charge Density/Solubility and Degree of Acetylation | p. 79 |
4.3.2 Improving the Physicochemical Characteristics of the Nanoparticulate Systems: Solubility, Aggregation and RES Uptake | p. 80 |
4.3.3 Targeting Mediated by Cell Surface Receptors | p. 81 |
4.3.4 Hydrophobic Modification: Protecting the DNA and Improving the Internalization Process | p. 83 |
4.4 Methods of Preparation of Chitosan Nanoparticles | p. 84 |
4.4.1 Complex Coacervation | p. 84 |
4.4.2 Crosslinking Methods | p. 86 |
4.4.2.1 Chemical Crosslinking | p. 86 |
4.4.2.2 Ionic Crosslinking or Ionic Gelation | p. 86 |
4.4.2.3 Emulsion Crosslinking | p. 87 |
4.4.2.4 Spray Drying | p. 88 |
4.4.2.5 Other Methods | p. 89 |
4.5 DNA Loading into Nano- and Microparticles of Chitosan | p. 91 |
4.6 DNA Release and Release Kinetics | p. 93 |
4.7 Preclinical Evidence of Chitosan-DNA Complex Efficacy | p. 95 |
4.8 Potential Clinical Applications of Chitosan-DNA in Gene Therapy | p. 97 |
4.9 Conclusion | p. 99 |
Acknowledgments | p. 99 |
References | p. 99 |
II Protein & Peptide-based Nanomaterials | p. 115 |
5 Plant Protein-based Nanoparticles | p. 117 |
5.1 Introduction | p. 117 |
5.2 Description of Plant Proteins | p. 118 |
5.2.1 Pea Seed Proteins | p. 119 |
5.2.2 Wheat Proteins | p. 119 |
5.3 Preparation of Protein Nanoparticles | p. 120 |
5.3.1 Preparation of Legumin and Vicilin Nanoparticles | p. 121 |
5.3.2 Preparation of Gliadin Nanoparticles | p. 122 |
5.4 Drug Encapsulation in Plant Protein Nanoparticles | p. 124 |
5.4.1 RA Encapsulation in Gliadin Nanoparticles | p. 124 |
5.4.2 VE Encapsulation in Gliadin Nanoparticles | p. 125 |
5.4.3 Lipophilic, Hydrophilic or Amphiphilic Drug Encapsulation | p. 126 |
5.5 Preparation of Ligand-Gliadin Nanoparticle Conjugates | p. 127 |
5.6 Bioadhesive Properties of Gliadin Nanoparticles | p. 129 |
5.6.1 Ex Vivo Studies with Gastrointestinal Mucosal Segments | p. 130 |
5.6.2 In Vivo Studies with Laboratory Animals | p. 131 |
5.7 Future Perspectives | p. 135 |
5.7.1 Size Optimization | p. 135 |
5.7.2 Immunization in Animals | p. 136 |
5.8 Conclusion | p. 137 |
References | p. 137 |
6 Peptide Nanoparticles | p. 145 |
6.1 Introduction | p. 145 |
6.2 Starting Materials for the Preparation of Nanoparticles | p. 146 |
6.3 Preparation Methods | p. 148 |
6.3.1 Nanoparticle Preparation by Emulsion Techniques | p. 148 |
6.3.1.1 Emulsion Technique for the Preparation of Albumin-based Microspheres and Nanoparticles | p. 148 |
6.3.1.2 Emulsion Technique for the Preparation of Gelatin-based Microspheres and Nanoparticles | p. 151 |
6.3.1.3 Emulsion Technique for the Preparation of Casein-based Microspheres and Nanoparticles | p. 153 |
6.3.2 Nanoparticle Preparation by Coacervation | p. 154 |
6.3.2.1 Complex Coacervation Techniques for the Preparation of Nanoparticles | p. 154 |
6.3.2.2 Simple Coacervation (Desolvation) Techniques for the Preparation of Nanoparticles | p. 155 |
6.4 Basic Characterization Techniques for Peptide Nanoparticles | p. 159 |
6.5 Drug Targeting with Nanoparticles | p. 161 |
6.5.1 Passive Drug Targeting with Particle Systems | p. 163 |
6.5.2 Active Drug Targeting with Particle Systems | p. 163 |
6.5.3 Surface Modifications of Protein-based Nanoparticles | p. 164 |
6.5.4 Surface Modification by Different Hydrophilic Compounds | p. 164 |
6.5.5 Surface Modification by Polyethylene Glycol (PEG) Derivatives | p. 165 |
6.5.6 Surface Modification by Drug-targeting Ligands | p. 166 |
6.5.7 Different Surface Modification Strategies | p. 168 |
6.6 Applications as Drug Carriers and for Diagnostic Purposes | p. 169 |
6.6.1 Protein-based Nanoparticles in Gene Therapy | p. 170 |
6.6.2 Parenteral Application Route | p. 172 |
6.6.2.1 Preclinical Studies with Protein-based Particles | p. 172 |
6.6.2.2 Clinical Studies with Protein-based Particles | p. 172 |
6.6.3 Topical Application of Protein-based Particles | p. 174 |
6.6.4 Peroral Application of Protein-based Particles | p. 175 |
6.7 Immunological Reactions with Protein-based Microspheres | p. 175 |
6.8 Concluding Remarks | p. 176 |
References | p. 176 |
7 Albumin Nanoparticles | p. 185 |
7.1 Introduction | p. 185 |
7.2 Serum Albumin | p. 186 |
7.3 Preparation of Albumin Nanoparticles | p. 187 |
7.3.1 "Conventional" Albumin Nanoparticles | p. 188 |
7.3.1.1 Preparation of Albumin Nanoparticles by Desolvation or Coacervation | p. 189 |
7.3.1.2 Preparation of Albumin Nanoparticles by Emulsification | p. 192 |
7.3.1.3 Other Techniques to Prepare Albumin Nanoparticles | p. 193 |
7.3.2 Surface-modified Albumin Nanoparticles | p. 193 |
7.3.3 Drug Encapsulation in Albumin Nanoparticles | p. 194 |
7.4 Biodistribution of Albumin Nanoparticles | p. 196 |
7.5 Pharmaceutical Applications | p. 198 |
7.5.1 Albumin Nanoparticles for Diagnostic Purposes | p. 198 |
7.5.1.1 Radiopharmaceuticals | p. 198 |
7.5.1.2 Echo-contrast Agents | p. 199 |
7.5.2 Albumin Nanoparticles as Carriers for Oligonucleotides and DNA | p. 199 |
7.5.3 Albumin Nanoparticles in the Treatment of Cancer | p. 201 |
7.5.3.1 Fluorouracil and Methotrexate Delivery | p. 201 |
7.5.3.2 Paclitaxel Delivery | p. 202 |
7.5.3.3 Albumin Nanoparticles in Suicide Gene Therapy | p. 203 |
7.5.4 Magnetic Albumin Nanoparticles | p. 204 |
7.5.5 Albumin Nanoparticles for Ocular Drug Delivery | p. 205 |
7.5.5.1 Topical Drug Delivery | p. 205 |
7.5.5.2 Intravitreal Drug Delivery | p. 205 |
7.6 Concluding Remarks | p. 207 |
References | p. 208 |
8 Nanoscale Patterning of S-Layer Proteins as a Natural Self-assembly System | p. 219 |
8.1 Introduction | p. 219 |
8.2 General Properties of S-Layers | p. 220 |
8.2.1 Structure, Isolation, Self-Assembly and Recrystallization | p. 220 |
8.2.2 Chemistry and Molecular Biology | p. 221 |
8.2.3 S-Layers as Carbohydrate-binding Proteins | p. 223 |
8.3 Nanoscale Patterning of S-Layer Proteins | p. 224 |
8.3.1 Properties of S-Layer Proteins Relevant for Nanoscale Patterning | p. 224 |
8.3.2 Immobilization of Functionalities by Chemical Methods | p. 225 |
8.3.3 Patterning by Genetic Approaches | p. 226 |
8.3.3.1 The S-Layer Proteins SbsA, SbsB and SbsC | p. 226 |
8.3.3.2 S-Layer Fusion Proteins | p. 228 |
8.4 Spatial Control over S-Layer Reassembly | p. 241 |
8.5 S-Layers as Templates for the Formation of Regularly Arranged Nanoparticles | p. 242 |
8.5.1 Binding of Molecules and Nanoparticles to Functional Domains | p. 242 |
8.5.2 In Situ Synthesis of Nanoparticles on S-Layers | p. 244 |
8.6 Conclusions and Outlook | p. 244 |
Acknowledgments | p. 245 |
References | p. 245 |
III Pharmaceutically Important Nanomaterials | p. 253 |
9 Methods of Preparation of Drug Nanoparticles | p. 255 |
9.1 Introduction | p. 255 |
9.2 Structures of Drug Nanoparticles | p. 257 |
9.3 Thermodynamic Approaches | p. 257 |
9.3.1 Lipid-based Pharmaceutical Nanoparticles | p. 258 |
9.3.2 What is a Lipid? | p. 259 |
9.3.3 Liquid Crystalline Phases of Hydrated Lipids with Planar and Curved Interfaces | p. 260 |
9.3.4 Oil-in-water-type Lipid Emulsion | p. 261 |
9.3.5 Liposomes | p. 261 |
9.3.6 Cubosomes and Hexosomes | p. 262 |
9.3.7 Other Lipid-based Pharmaceutical Nanoparticles | p. 263 |
9.4 Mechanical Approaches | p. 264 |
9.4.1 Types of Processing | p. 264 |
9.4.2 Characteristics of Wet Comminution | p. 266 |
9.4.3 Drying of Liquid Nanodispersions | p. 267 |
9.5 SCF Approaches | p. 270 |
9.5.1 SCF Characteristics | p. 270 |
9.5.2 Classification of SCF Particle Formation Processes | p. 271 |
9.5.3 RESS | p. 272 |
9.5.4 SAS | p. 273 |
9.5.5 SEDS | p. 274 |
9.6 Electrostatic Approaches | p. 275 |
9.6.1 Electrical Potential and Interfaces | p. 275 |
9.6.2 Electrospraying | p. 277 |
References | p. 280 |
10 Production of Biofunctionalized Solid Lipid Nanoparticles for Site-specific Drug Delivery | p. 287 |
10.1 Introduction | p. 287 |
10.2 Concept of Differential Adsorption | p. 289 |
10.3 Production of SLN | p. 292 |
10.4 Functionalization by Surface Modification | p. 294 |
10.5 Conclusions | p. 298 |
References | p. 299 |
11 Biocompatible Nanoparticulate Systems for Tumor Diagnosis and Therapy | p. 304 |
11.1 Introduction | p. 304 |
11.2 Nanoscale Particulate Systems and their Building Blocks/Components | p. 305 |
11.2.1 Dendrimers | p. 305 |
11.2.2 Buckyballs and Buckytubes | p. 307 |
11.2.3 Quantum Dots | p. 309 |
11.2.4 Polymeric Micelles | p. 310 |
11.2.5 Liposomes | p. 310 |
11.3 Biodegradable Nanoparticles | p. 312 |
11.3.1 Preparation of Nanoparticles | p. 313 |
11.4 Biodegradable Optical Nanoparticles | p. 314 |
11.4.1 Optical Nanoparticles as a Potential Technology for Tumor Diagnosis | p. 314 |
11.4.2 Optical Nanoparticles as a Potential Technology for Tumor Treatment | p. 315 |
11.5 Optical Imaging and PDT | p. 317 |
11.5.1 Optical Imaging | p. 317 |
11.5.1.1 Fluorescence-based Optical Imaging | p. 317 |
11.5.1.2 NIR Fluorescence Imaging | p. 317 |
11.5.1.3 NIR Dyes for Fluorescence Imaging | p. 318 |
11.5.2 PDT | p. 318 |
11.5.2.1 Basis of PDT | p. 319 |
11.5.2.2 Photosensitizers for PDT | p. 320 |
11.5.3 ICG: An Ideal Photoactive Agent for Tumor Diagnosis and Treatment | p. 320 |
11.5.3.1 Clinical Uses of ICG | p. 320 |
11.5.3.2 Structure and Physicochemical Properties of ICG | p. 321 |
11.5.3.3 Binding Properties of ICG | p. 321 |
11.5.3.4 Metabolism, Excretion and Pharmacokinetics of ICG | p. 322 |
11.5.3.5 Toxicity of ICG | p. 322 |
11.5.3.6 Tumor Imaging with ICG | p. 322 |
11.5.3.7 PDT with ICG | p. 323 |
11.5.3.8 Limitations of ICG for Tumor Diagnosis and Treatment | p. 324 |
11.5.3.9 Recent Approaches for Improving the Blood Circulation Time and Uptake of ICG by Tumors | p. 325 |
11.5.3.10 Recent Approaches for ICG Stabilization In Vitro | p. 326 |
11.6 PLGA-based Nanoparticulate Delivery System for ICG | p. 327 |
11.6.1 Rationale of Using a PLGA-based Nanoparticulate Delivery System for ICG | p. 327 |
11.6.2 In Vivo Pharmacokinetics of ICG Solutions and Nanoparticles | p. 331 |
11.7 Conclusions and Future Work | p. 336 |
References | p. 338 |
12 Nanoparticles for Crossing Biological Membranes | p. 349 |
12.1 Introduction | p. 349 |
12.2 Cell Membranes | p. 350 |
12.2.1 Functions of Biological Membranes | p. 351 |
12.2.2 Kinetic and Thermodynamic Aspects of Biological Membranes | p. 352 |
12.3 Problems of Drugs Crossing through Biological Membranes | p. 354 |
12.3.1 Through the Skin | p. 354 |
12.3.1.1 Mechanical Irritation of Skin | p. 355 |
12.3.1.2 Low-voltage Electroporation of the Skin | p. 355 |
12.3.2 Through the BBB | p. 357 |
12.3.2.1 Small Drugs | p. 359 |
12.3.2.1.1 Limitations of Small Drugs | p. 359 |
12.3.2.2 Peptide Drug Delivery via SynB Vectors | p. 360 |
12.3.3 GI Barrier | p. 360 |
12.3.3.1 Intestinal Translocation and Disease | p. 361 |
12.4 Nanoparticulate Drug Delivery | p. 362 |
2.4.1 Skin | p. 363 |
12.4.1.1 Skin as Semipermeable Nanoporous Barrier | p. 363 |
12.4.1.2 Hydrophilic Pathway through the Skin Barrier | p. 363 |
12.4.2 Solid-Lipid Nanoparticles (SLN) Skin Delivery | p. 364 |
12.4.2.1 Chemical Stability of SLN | p. 364 |
12.4.2.2 In Vitro Occlusion of SLN | p. 365 |
12.4.2.3 In Vivo SLN: Occlusion, Elasticity and Wrinkles | p. 365 |
12.4.2.4 Active Compound Penetration into the Skin | p. 365 |
12.4.2.5 Controlled Release of Cosmetic Compounds | p. 365 |
12.4.2.6 Novel UV Sunscreen System Using SLN | p. 366 |
12.4.3 Polymer-based Nanoparticulate Delivery to the Skin | p. 366 |
12.4.4 Subcutaneous Nanoparticulate Antiepileptic Drug Delivery | p. 366 |
12.4.5 Nanoparticulate Anticancer Drug Delivery | p. 367 |
12.4.5.1 Paclitaxel | p. 368 |
12.4.5.2 Doxorubicin | p. 368 |
12.4.5.3 5-Fluorouracil (5-FU) | p. 369 |
12.4.5.4 Antineoplastic Agents | p. 369 |
12.4.5.5 Gene Delivery | p. 369 |
12.4.5.6 Breast Cancer | p. 370 |
12.4.6 Nanofibers Composed of Nonbiodegradable Polymer | p. 370 |
12.4.6.1 Electrostatic Spinning | p. 371 |
12.4.6.2 Scanning Electron Microscopy | p. 371 |
12.4.6.3 Differential Scanning Calorimetry (DSC) | p. 371 |
12.5 Nanoparticulate Delivery to the BBB | p. 371 |
12.5.1 Peptide Delivery to the BBB | p. 372 |
12.5.1.1 Peptide Conjugation through a Disulfide Bond | p. 373 |
12.5.2 Biodegradable Polymer Based Nanoparticulate Delivery to BBB | p. 373 |
12.5.3 Nanoparticulate Gene Delivery to the BBB | p. 374 |
12.5.4 Mechanism of Nanoparticulate Drug Delivery to the BBB | p. 375 |
12.5.5 Nanoparticulate Thiamine-coated Delivery to the BBB | p. 376 |
12.5.6 Nanoparticle Optics and Living Cell Imaging | p. 376 |
12.6 Oral Nanoparticulate Delivery | p. 378 |
12.6.1 Lectin-conjugated Nanoparticulate Oral Delivery | p. 379 |
12.6.2 Oral Peptide Nanoparticulate-based Delivery | p. 380 |
12.6.3 Polymer-Based Oral Peptide Nanoparticulate Delivery | p. 381 |
12.6.3.1 Polyacrylamide Nanospheres | p. 381 |
12.6.3.2 Poly(alkyl cyanoacrylate) PACA Nanocapsules | p. 381 |
12.6.3.3 Derivatized Amino Acid Microspheres | p. 382 |
12.6.4 Lymphatic Oral Nanoparticulate Delivery | p. 382 |
12.6.5 Oral Nanosuspension Delivery | p. 383 |
12.6.6 Mucoadhesion of Nanoparticles after Oral Administration | p. 384 |
12.6.7 Protein Nanoparticulate Oral Delivery | p. 384 |
References | p. 385 |
Index | p. 394 |