Preface .................................................... XIV
List of Contributors ...................................... XVII
I DNA-based Nanomaterials ...................................... 1
1 Self-assembled DNA Nanotubes ................................. 3
Thorn LaBean and Sung Ha Park
1.1 Introduction ............................................ 3
1.2 DNA Nanotubes Self-assembled from DX Tiles .............. 4
1.3 3DAE-E DX Tile Nanotubes ................................ 5
1.4 DAE-0 DX Tile Nanotubes ................................. 9
1.5 TX Tile Nanotubes ...................................... 11
1.6 4×4 Tile Nanotubes ..................................... 34
1.7 6HB Tile Nanotubes ..................................... 16
1.8 Applications ........................................... 18
1.9 Summary and Perspectives ............................... 19
References .................................................. 20
2 Nucleic Acid Nanoparticles .................................. 23
Guy Zuber, Bénédicte Pons and Andrew W. Fraley
2.1 Introduction ........................................... 23
2.2 The Chemical and Physical Properties of Therapeutic
DNA .................................................... 25
2.3 Preparation of Nucleic Acid Nanoparticles: Synthesis
and Characterization ................................... 27
2.3.1 Rationale ....................................... 27
2.3.2 Synthesis, Characterization and Optimization
of Surfactants .................................. 31
2.3.3 Organization of the Surfactant-DNA Complexes .... 35
2.3.4 Quantification of the Stability of Surfactant-
DNA Complexes ................................... 35
2.4 DNA Functionalization for Cell Recognition and
Internalization
2.4.1 Strategies for Functionalization ................ 37
2.4.2 Intercalation ................................... 38
2.4.3 Triple Helix Formation with
Oligodeoxyribonucleotides ....................... 39
2.4.4 Peptide Nucleic Acids (PNAs) .................... 41
2.4.5 Interactions of DNA with Fusion Proteins ........ 42
2.4.6 Agents that Bind to the Minor Groove ............ 43
2.5 DNA Nanoparticles: Sophistication for Cell
Recognition and Internalization ........................ 43
2.5.1 Preparation of DNA Nanoparticles Enveloped
with a Protective Coat and Cell
Internalization Elements ........................ 43
2.5.2 Biomedical Application: Cell Targeting and
Internalization Properties of Folate-PEG-
coated Nanoparticles ............................ 46
2.6 Concluding Remarks ..................................... 46
References .................................................. 47
3 Lipoplexes .................................................. 51
Sarah Weisman
3.1 Introduction ........................................... 51
3.2 DNA Lipoplexes ......................................... 51
3.2.1 Composition ..................................... 51
3.2.2 Nanostructure and Microstructure ................ 52
3.2.3 Lipofection Efficiency .......................... 57
3.3 ODN Lipoplexes ......................................... 60
3.4 siRNA Lipoplexes ....................................... 62
Acknowledgments ............................................. 62
References .................................................. 62
4 DNA-Chitosan Nanoparticles for Gene Therapy: Current
Knowledge and Future Trends ................................. 68
Julio C. Fernandes, Marcio José Tiera and Françoise
M. Winnik
4.1 Introduction ........................................... 68
4.2 Chitosan as a Carrier for Gene Therapy ................. 69
4.2.1 Chitosan Chemistry .............................. 69
4.2.2 General Strategies for Chitosan Modification .... 71
4.2.3 Chitosan-DNA interactions: Transfection
Efficacy of Unmodified Chitosan ................. 71
4.3 Modified Chitosans: Strategies to Improve the
Transfection Efficacy .................................. 79
4.3.1 The Effects of Charge Density/Solubility and
Degree of Acetylation ........................... 79
4.3.2 Improving the Physicochemical Characteristics
of the Nanoparticulate Systems: Solubility.
Aggregation and RES Uptake ...................... 80
4.3.3 Targeting Mediated by Cell Surface Receptors .... 81
4.3.4 Hydrophobic Modification: Protecting the DNA
and Improving the Internalization Process ....... 83
4.4 Methods of Preparation of Chitosan Nanoparticles ....... 84
4.4.1 Complex Coacervation ............................ 84
4.4.2 Crosslinking Methods ............................ 86
4.5 DNA Loading into Nano- and Microparticles of
Chitosan ............................................... 97
4.6 DNA Release and Release Kinetics ....................... 93
4.7 Preclinical Evidence of Chitosan-DNA Complex
Efficacy ............................................... 95
4.8 Potential Clinical Applications of Chitosan-DNA in
Gene Therapy ........................................... 97
4.9 Conclusion ............................................. 99
Acknowledgments ............................................. 99
References .................................................. 99
II Protein & Peptide-based Nanomaterials ..................... 115
5 Plant Protein-based Nanoparticles .......................... 117
Anne-Marie Orecchioni, Cécile Duclairoir, Juan Manuel
Irache and Evelyne Nakache
5.1 Introduction .......................................... 117
5.2 Description of Plant Proteins ......................... 118
5.2.1 Pea Seed Proteins .............................. 119
5.2.2 Wheat Proteins ................................. 119
5.3 Preparation of Protein Nanoparticles .................. 120
5.3.1 Preparation of Legumin and Vicilin
Nanoparticles .................................. 121
5.3.2 Preparation of Gliadin Nanoparticles ........... 122
5.4 Drug Encapsulation in Plant Protein Nanoparticles ..... 124
5.4.1 RA Encapsulation in Gliadin Nanoparticles ...... 124
5.4.2 VE Encapsulation in Gliadin Nanoparticles ...... 125
5.4.3 Lipophilic, Hydrophilic or Amphiphilic Drug
Encapsulation .................................. 126
5.5 Preparation of Ligand-Gliadin Nanoparticle
Conjugates ............................................ 127
5.6 Bioadhesive Properties of Gliadin Nanoparticles ....... 129
5.6.1 Ex Vivo Studies with Gastrointestinal Mucosal
Segments ....................................... 130
5.6.2 In Vivo Studies with Laboratory Animals ........ 131
5.7 Future Perspectives ................................... 135
5.7.1 Size Optimization .............................. 135
5.7.2 Immunization in Animals ........................ 136
5.8 Conclusion ............................................ 137
References ................................................. 137
6 Peptide Nanoparticles ...................................... 145
Klaus Langer
6.1 Introduction .......................................... 145
6.2 Starting Materials for the Preparation of
Nanoparticles ......................................... 146
6.3 Preparation Methods ................................... 148
6.3.1 Nanoparticle Preparation by Emulsion
Techniques ..................................... 148
6.3.2 Nanoparticle Preparation by Coacervation ....... 154
6.4 Basic Characterization Techniques for Peptide
Nanoparticles ......................................... 159
6.5 Drug Targeting with Nanoparticles ..................... 161
6.5.1 Passive Drug Targeting with Particle Systems ... 163
6.5.2 Active Drug Targeting with Particle Systems .... 163
6.5.3 Surface Modifications of Protein-based
Nanoparticles .................................. 164
6.5.4 Surface Modification by Different Hydrophilic
Compounds ...................................... 164
6.5.5 Surface Modification by Polyethylene Glycol
(PEG) Derivatives .............................. 165
6.5.6 Surface Modification by Drug-targeting
Ligands ........................................ 166
6.5.7 Different Surface Modification Strategies ...... 168
6.6 Applications as Drug Carriers and for Diagnostic
Purposes .............................................. 169
6.6.1 Protein-based Nanoparticles in Gene Therapy .... 170
6.6.2 Parenteral Application Route ................... 172
6.6.3 Topical Application of Protein-based
Particles ...................................... 174
6.6.4 Peroral Application of Protein-based Particles 175
6.7 Immunological Reactions with Protein-based
Microspheres .......................................... 175
6.8 Concluding Remarks .................................... 176
References ................................................. 176
7 Albumin Nanoparticles ...................................... 185
Juan Manuel Irache and Socorro Espuelas
7.1 Introduction .......................................... 185
7.2 Serum Albumin ......................................... 186
7.3 Preparation of Albumin Nanoparticles .................. 787
7.3.1 "Conventional" Albumin Nanoparticles ........... 188
7.3.2 Surface-modified Albumin Nanoparticles ......... 193
7.3.3 Drug Encapsulation in Albumin Nanoparticles .... 194
7.4 Biodistribution of Albumin Nanoparticles .............. 196
7.5 Pharmaceutical Applications ........................... 198
7.5.1 Albumin Nanoparticles for Diagnostic
Purposes ....................................... 198
7.5.2 Albumin Nanoparticles as Carriers for
Oligonucleotides and DNA ....................... 199
7.5.3 Albumin Nanoparticles in the Treatment of
Cancer ......................................... 201
7.5.4 Magnetic Albumin Nanoparticles ................. 204
7.5.5 Albumin Nanoparticles for Ocular Drug
Delivery ....................................... 205
7.6 Concluding Remarks .................................... 207
References ................................................. 208
8 Nanoscale Patterning of S-Layer Proteins as a Natural
Self-assembly System ....................................... 219
Margit Sára, D. Рum, C. Huber, N. Ilk, M. Pleschberger
and U.B. Sleytr
8.1 Introduction .......................................... 219
8.2 General Properties of S-Layers ........................ 220
8.2.1 Structure, Isolation, Self-Assembly and
Recrystallization .............................. 220
8.2.2 Chemistry and Molecular Biology ................ 221
8.2.3 S-Layers as Carbohydrate-binding Proteins ...... 223
8.3 Nanoscale Patterning of S-Layer Proteins .............. 224
8.3.1 Properties of S-Layer Proteins Relevant for
Nanoscale Patterning ........................... 224
8.3.2 Immobilization of Functionalities by Chemical
Methods ........................................ 225
8.3.3 Patterning by Genetic Approaches ............... 226
8.4 Spatial Control over S-Layer Reassembly ............... 241
8.5 S-Layers as Templates for the Formation of Regularly
Arranged Nanoparticles ................................ 242
8.5.1 Binding of Molecules and Nanoparticles to
Functional Domains ............................. 242
8.5.2 In Situ Synthesis of Nanoparticles on
S-Layers ....................................... 244
8.6 Conclusions and Outlook ............................... 244
Acknowledgments ............................................ 245
References ................................................. 245
III Pharmaceutical Important Nanomaterials ................... 253
9 Methods of Preparation of Drug Nanoparticles ............... 255
Jonghwi Lee, Gio-Bin Lim and Hesson Chung
9.1 Introduction .......................................... 255
9.2 Structures of Drug Nanoparticles ...................... 257
9.3 Thermodynamic Approaches .............................. 257
9.3.1 Lipid-based Pharmaceutical Nanoparticles ....... 258
9.3.2 What is a Lipid? ............................... 259
9.3.3 Liquid Crystalline Phases of Hydrated Lipids
with Planar and Curved Interfaces .............. 260
9.3.4 Oil-in-water-type Lipid Emulsion ............... 261
9.3.5 Liposomes ...................................... 261
9.3.6 Cubosomes and Hexosomes ........................ 262
9.3.7 Other Lipid-based Pharmaceutical
Nanoparticles .................................. 263
9.4 Mechanical Approaches ................................. 264
9.4.1 Types of Processing ............................ 264
9.4.2 Characteristics of Wet Comminution ............. 266
9.4.3 Drying of Liquid Nanodispersions ............... 267
9.5 SCF Approaches ........................................ 270
9.5.1 SCF Characteristics ............................ 270
9.5.2 Classification of SCF Particle Formation
Processes ...................................... 271
9.5.3 RESS ........................................... 272
9.5.4 SAS ............................................ 273
9.5.5 SEDS ........................................... 274
9.6 Electrostatic Approaches .............................. 275
9.6.1 Electrical Potential and Interfaces ............ 275
9.6.2 Electrospraying ................................ 277
References ................................................. 280
10 Production of Biofunctionalized Solid Lipid Nanoparticles
for Site-specific Drug Delivery ............................ 287
Rainer H. Müller, Eliana B. Souto, Torsten Cöppert and
Sven Gohla
10.1 Introduction .......................................... 287
10.2 Concept of Differential Adsorption .................... 289
10.3 Production of SLN ..................................... 292
10.4 Functionalization by Surface Modification ............. 294
10.5 Conclusions ........................................... 298
References ................................................. 299
11 Biocompatible Nanoparticulate Systems for Tumor Diagnosis
and Therapy ................................................ 304
Mostafa Sadoqi, Sunil Kumar, Cesar Lau-Cam and Vishal
Saxena
11.1 Introduction .......................................... 304
11.2 Nanoscale Particulate Systems and their Building
Blocks Components ..................................... 305
11.2.1 Dendrimers ..................................... 305
11.2.2 Buckyballs and Buckytubes ...................... 307
11.2.3 Quantum Dots ................................... 309
11.2.4 Polymeric Micelles ............................. 310
11.2.5 Liposomes ...................................... 310
11.3 Biodegradable Nanoparticles ........................... 312
11.3.1 Preparation of Nanoparticles ................... 313
11.4 Biodegradable Optical Nanoparticles ................... 314
11.4.1 Optical Nanoparticles as a Potential
Technology for Tumor Diagnosis ................. 314
11.4.2 Optical Nanoparticles as a Potential
Technology for Tumor Treatment ................. 315
11.5 Optical Imaging and PDT ............................... 317
11.5.1 Optical Imaging ................................ 317
11.5.2 PDT ............................................ 318
11.5.3 ICG: An Ideal Photoactive Agent for Tumor
Diagnosis and Treatment ........................ 320
11.6 PLGA-based Nanoparticulate Delivery System for ICG .... 327
11.6.1 Rationale of Using a PLGA-based
Nanoparticulate Delivery System for ICG ........ 327
11.6.2 In Vivo Pharmacokinetics of ICG Solutions and
Nanoparticles .................................. 331
11.7 Conclusions and Future Work ........................... 336
References ................................................. 338
12 Nanoparticles for Crossing Biological Membranes ............ 349
R. Pawar, A. Avramoff and A.J. Domb
12.1 Introduction .......................................... 349
12.2 Cell Membranes ........................................ 350
12.2.1 Functions of Biological Membranes .............. 351
12.2.2 Kinetic and Thermodynamic Aspects of
Biological Membranes ........................... 352
12.3 Problems of Drugs Crossing through Biological Membranes 354
12.3.1 Through the Skin ............................... 354
12.3.2 Through the BBB ................................ 357
12.3.3 GI Barrier ..................................... 360
12.4 Nanoparticulate Drug Delivery ......................... 362
12.4.2 Solid-Lipid Nanoparticles (SLN) Skin
Delivery ....................................... 364
12.4.3 Polymer-based Nanoparticulate Delivery to the
Skin ........................................... 366
12.4.4 Subcutaneous Nanoparticulate Antiepileptic
Drug Delivery .................................. 366
12.4.5 Nanoparticulate Anticancer Drug Delivery ....... 367
12.4.6 Nanofibers Composed of Nonbiodegradable
Polymer ........................................ 370
12.5 Nanoparticulate Delivery to the BBB ................... 371
12.5.1 Peptide Delivery to the BBB .................... 372
12.5.2 Biodegradable Polymer Based Nanoparticulate
Delivery to BBB ................................ 373
12.5.3 Nanoparticulate Gene Delivery to the BBB ....... 374
12.5.4 Mechanism of Nanoparticulate Drug Delivery to
the BBB ........................................ 375
12.5.5 Nanoparticulate Thiamine-coated Delivery to
the BBB ........................................ 376
12.5.6 Nanoparticle Optics and Living Cell Imaging .... 376
12.6 Oral Nanoparticulate Delivery ......................... 378
12.6.1 Lectin-conjugated Nanoparticulate Oral
Delivery ....................................... 379
12.6.2 Oral Peptide Nanoparticulate-based Delivery .... 380
12.6.3 Polymer-Based Oral Peptide Nanoparticulate
Delivery ....................................... 381
12.6.4 Lymphatic Oral Nanoparticulate Delivery ........ 382
12.6.5 Oral Nanosuspension Delivery ................... 383
12.6.6 Mucoadhesion of Nanoparticles after Oral
Administration ................................. 384
12.6.7 Protein Nanoparticulate Oral Delivery .......... 384
References ................................................ 385
Index ...................................................... 394
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