Particulate Technology for Delivery of Therapeutics (eBook)

Prof. Sougata Jana is working at the Department of Pharmaceutics, Gupta College of Technological Sciences, under Maulana Abul Kalam Azad University of Technology (formerly known as West Bengal University of Technology), West Bengal, India. He is an M. Pharm (Pharmaceutics) from Biju Patnaik University of Technology (BPUT), Odisha, India. He is engaged in research for 9 years and that of teaching for 8 years. He qualified GATE examination in the year 2005. He received ‘Gold Medal’ from West Bengal University of Technology (WBUT), Kolkata for standing first at UG level. IPA Bengal branch, Kolkata, India conferred him ‘M.N Dev Memorial award’ for securing the highest marks in the state of West Bengal in the year 2005. He bragged ‘Best Poster Presentation Award’ at 21st West Bengal State Science and Technology Congress-2014, Burdwan, West Bengal, India. He published 24 research papers in different national and international peer reviewed journals.  He is edited in one book ‘ADVANCE Pharmaceutical Analytical Technique’ under Pharmamedix India Publication Pvt. Ltd. Twenty chapters are also in his credit in Wiley VCH, CRC Press, Taylor & Francis group, Elsevier, etc.. He is reviewer of various international journals such as Elsevier, Wiley, Springer, Taylor and Francis, Dove Press etc. He is a life member of Association of Pharmaceutical Teachers of India (APTI). He successfully guided 15 postgraduate students for their research projects. He is working in the field of drug delivery science and technology including modification of synthetic and natural biopolymers, microparticles, nanoparticles, semisolids and interpenetrating network (IPN) system for controlled drug delivery.Prof. Subrata Jana obtained his PhD in organic chemistry from Indian Institute of Engineering Science and Technology (IIEST), Shibpur, India. His doctoral work was based on design and synthesis of abiotic receptors for the recognition of biologically active neutral molecules and ions along with development synthetic methodologies. He is also studied the recognition process in solution phase as well as in solid state. Overall he extensively studied on supramolecular behaviour of the host-guest interaction. Besides, he has worked on the development of synthetic methodologies for substituted heterocyclics like pyrimidines, naphthyridines, quinoline and diazepines etc. by exploiting microwave protocol for green chemical synthesis.  After that he moved to University of Victoria, Canada, to work with Dr Fraser Hof on supramolecular and medicinal chemistry as a post-doctoral fellow, where he worked on the synthesis of different receptors targeting N-methylated protein residue along with anions. He then worked further with Dr Kenneth J Woycechowsky at University of Utah, USA, on protein engineering and enzyme catalysis as post-doctoral research associate. He studied of enzyme activity when it is encapsulated inside the capsid which is a nano carrier and an excellent delivery vehicle for important biological substrate including drug molecules. Presently, he is working as Associate Professor at Department of Chemistry, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India and his current research focuses on design and synthesis of artificial receptors for the recognition of anions, cations and N-methylated protein residue. He is also working on biodegradable polymeric based carrier systems for the delivery of drug molecules by collaboration with pharmaceutical scientist. So far he has published ~40 research paper in peer reviewed international journals and contributed more than 10 book chapters in different edited books published by internationally renowned publishers. He also serve as editorial board member for the Journal of PharmaSciTech (ISSN: 2231 3788) and International Journal of Scientific and Engineering Research (ISSN: 2229-5518) as well as reviewer for International Journal of Biological Macromolecule (Elsevier), Journal of PharmaSciTech and Current Pharmaceutical Design (Bentham).

Preface 5
Contents 8
About the Editors 10
List of Contributors 12
1 Introduction to Novel Therapeutic Carriers 15
Abstract 15
1 Introduction 16
2 Type of New Drug Carriers Systems 17
2.1 Transdermal Drug Delivery System 18
2.2 Carrier-Based Delivery Systems 19
2.3 Variable Release Delivery Systems 21
2.3.1 Osmotic Pump-Based Drug Delivery Systems 21
2.3.2 Reservoir-Based System 22
2.3.3 Matrix-Based Drug Delivery System 23
3 Preparation of Particulate Drug Delivery Systems 24
3.1 Dispersion Method 25
3.2 Solvent Evaporation Method 25
3.3 Emulsification or Solvent Diffusion Method 25
3.4 Coacervation Method 25
3.5 Polymerization Method 26
3.6 Spray Drying and Congealing 27
3.7 Emulsification-Cross-Linking Method 27
3.8 Reverse Micellar Method 28
3.9 Supercritical Method 28
4 Release Kinetics from Nondegradable Polymeric Matrices 28
5 Release Kinetics from Biodegradable Polymeric Matrices 29
6 Concluding Remarks 33
References 33
2 The Development and Achievement of Polymeric Nanoparticles for Cancer Drug Treatment 39
Abstract 39
1 Introduction 40
1.1 Physiological Conditions of Tumor Tissues 41
1.2 Rationale of Cancer Nanotechnology 42
1.3 Important Considerations in Nanoparticle-Based Delivery for Cancer Treatment 43
1.3.1 Passive Targeting of Nanoparticles: Enhanced Permeability and Retention (EPR) Effect 44
1.3.2 Active Targeting of Nanoparticles 45
2 Polymeric Nanocarriers for Therapeutic Applications in Cancer 45
2.1 Polymeric Micelles for Therapeutic Applications in Cancer 46
2.1.1 Doxorubicin (DOX) Conjugated Polymeric Micelles 46
2.1.2 Paclitaxel (PTX) Conjugated Polymeric Micelles 51
2.1.3 Other Chemotherapeutic Drugs Conjugated Polymeric Micelles 53
2.2 Polymeric Nanoparticles for Therapeutic Applications in Cancer 55
2.2.1 PTX-Loaded Polymericnano Particles 55
2.2.2 DOX-Loaded Polymeric Nanoparticles 61
2.2.3 Other Chemotherapeutic Drugs Loaded Polymericnano Particles 62
3 Stimuli-responsive Polymeric Nanocarriers 63
3.1 Endogenous Stimuli-responsive Polymeric Nanoparticles and Micelles 63
3.2 Exogenous Stimuli-Responsive Polymeric Nanoparticles and Micelles 75
3.3 Multiple Stimuli-Responsive Polymeric Nanoparticles and Micelles 77
4 Conclusions 78
Acknowledgements 81
References 81
3 Nanotechnology-Based Immunotherapeutic Strategies for the Treatment of Cancer 97
Abstract 97
1 Introduction 98
2 Immunotherapies 99
3 Cancer and Immune System 100
3.1 Limitations of Existing Cancer Therapies 101
4 Basics and Strategies of Cancer Immunotherapy 102
4.1 Monoclonal Antibodies (mAbs) 104
4.2 Cancer Vaccines 105
4.3 Peptide Vaccines 105
4.4 Tumor Cell Based Vaccines 105
4.5 DNA Vaccines 106
4.6 Vector-Based Vaccines 106
4.7 Dendritic Cell Based Immunotherapy 107
4.8 Immune Checkpoint Inhibitors 107
4.9 Nonspecific Immunotherapies 107
4.9.1 Nano-immunotherapy 107
5 Challenges for Cancer Immunotherapy 108
5.1 Aging Immune System 108
5.2 Tumor-Induced Immunosuppression and Immune Evasion 109
6 Nanocarrier(s)-Based Delivery Approaches for Cancer Immunotherapy 109
6.1 Nanoparticles as a Versatile Platform for Cancer Immunotherapy 116
6.2 Delivery of Nonspecific DC Stimuli (Adjuvants) to Tumor-Draining Lymph Nodes (TDLNs) 117
6.3 Co-delivery of Antigen and Adjuvant 118
7 Inorganic Nanoparticles in Cancer Immunotherapy 119
7.1 Magnetite Nanoparticles (MNPs) 119
7.2 Silica Materials 120
7.3 Gold Nanoparticle (AuNPs) 121
8 Lipid-Based Nanocarriers(s) for Cancer Immunotherapy 121
9 Conclusion 123
References 124
4 Nano-therapeutic Approaches for Targeting Cancer Stem Cells 130
Abstract 130
1 Introduction 131
2 Hurdles to the Delivery of Drugs to CSCs 132
3 Current Status of CSCs Therapy 134
3.1 Targeting of Specific Cell Surface Molecules 135
3.2 Targeting of the Tumor Microenvironment of CSCs 136
3.3 Targeting ATP-Binding Cassette (ABC) Transporters 138
3.4 Poly-aptamer-Drug Approach 139
3.5 Nanometric Drug Delivery Platforms 141
4 Conclusion 145
References 145
5 Dendrimers as Nanostructured Therapeutic Carriers 151
Abstract 151
1 Introduction 152
2 Ocular Therapeutics 154
3 Brain-Targeted Therapeutics 159
4 Tumor-Targeted Therapeutics 162
5 Oral Therapeutics 168
6 Conclusion 171
References 171
6 Chitosan-Based Nanoparticulate Systems: Implication Towards Therapeutics Application 179
Abstract 179
1 Introduction 180
2 Properties of Chitosan the Polymer 181
2.1 Structure 181
2.2 Source and Molecular Weight of Chitosan 182
2.3 Degree of Deacetylation of Chitosan 182
2.4 Solubility of Chitosan 183
3 Chitosan: Ideal Choice for Particulate System 183
3.1 Methods of Preparation of Chitosan Nano- and Microparticles 184
3.1.1 Emulsion Cross-Linking for Preparation of Chitosan Nanoparticles 184
3.1.2 Thermal Cross-Linking of Chitosan Particles 186
3.1.3 Coacervation/Precipitation for Preparation of Chitosan Nanoparticles 186
3.1.4 Spray Drying 187
3.1.5 Emulsion-Droplet Coalescence Method 188
3.1.6 Ionic Gelation 188
3.1.7 Reverse Micellar Method 189
3.1.8 Sieving Method 191
3.2 Derivatives of Chitosan Used for Particulate Systems 191
3.2.1 Improved Water Solubility Due to N-Alkylation/Improved Cationic Properties 191
3.2.2 Amphiphilic Chitosan Derivatives 196
3.2.3 Improved Mucoadhesive and Permeation Properties 197
3.2.4 Increased Transfection Efficiency 197
3.2.5 Biomedical Imaging 199
4 Chitosan-Based Particles for Delivery of Biomolecules 200
4.1 DNA 200
4.1.1 Factors Affecting DNA Delivery via Chitosan Particulate Systems 201
4.2 siRNA 206
4.2.1 Factor Affecting siRNA Delivery via Chitosan Particulate Systems 206
4.3 Peptides/Proteins via Chitosan Particulate Systems 210
5 Effect of Route of Administration 214
5.1 Effect of Route of Administration on DNA Delivery 214
5.2 Effect of Route of Administration on siRNA Delivery 215
5.3 Effect of Route of Administration on Peptides/Proteins Delivery 216
6 Chitosan-Based Formulations for Vaccine Delivery 218
7 Biodistribution of Chitosan Particulate System 221
8 In Vitro and In Vivo Toxicity 222
9 Stability of Chitosan 223
10 Conclusion 224
References 224
7 Carboxymethyl Polysaccharide-Based Multiunit Hydrogel Systems for Drug Delivery 238
Abstract 238
1 Introduction 239
2 Carboxymethylation of Polysaccharides 241
2.1 Dry Method 241
2.2 Wet Method 242
3 Preparation of Hydrogel Particles 242
3.1 Nanoprecipitation and Dialysis Cross-Linking 242
3.2 Jeffamine/ POX Cross-Linking 243
3.3 Hydrophobization of Carboxymethyl Derivative 243
3.4 Ionotropic Gelation Method 244
3.5 Emulsion Cross-Linking 245
3.6 Surfactant-Facilitated Reticulation 245
3.7 Simultaneous or Sequential Cross-Linking 245
4 Drug Delivery Applications 246
4.1 Hydrogel Particles of Single CM-Biopolymer 246
4.1.1 Xanthan Gum 246
4.1.2 Guar Gum 247
4.1.3 Locust Bean Gum (LBG) 248
4.1.4 Pullulan 248
4.2 Interpenetrating Particles of Dual Biopolymers 249
4.2.1 Xanthan Gum IPNs 249
4.2.2 Guar Gum and Other Polysaccharides 249
4.2.3 Locust Bean Gum and Others 250
4.2.4 Pullulan and Others 251
4.3 Grafted CM-Polysaccharide Hydrogel Particles 252
4.3.1 Xanthan Gum-Based Grafting 252
4.3.2 Guar Gum Grafting 252
4.3.3 LBG Grafting 253
4.3.4 Pulluan Grafting 253
4.3.5 Curdlan-Based Graft Copolymers 254
5 Conclusion 256
References 257
8 Lipid Carriers: Role and Applications in Nano Drug Delivery 263
Abstract 263
1 Introduction 264
2 Mechanism of Lipid Carriers in Improved Drug Delivery 265
2.1 Oral Delivery 265
2.2 Topical Delivery 267
2.3 Pulmonary Delivery 267
2.4 Ophthalmic Delivery 267
3 Lipid Nanoparticles 268
3.1 Solid Lipid Nanoparticles 268
3.1.1 Selection of Excipients 269
3.1.2 Preparation Techniques 270
High-Pressure Homogenization 270
Solvent Emulsification-Evaporation Method 271
Solvent Diffusion Method 271
Solvent Injection Method 271
Double Emulsion Method 272
Micro Emulsion-Based Method 272
High Shear Homogenization/Ultra-Sonication 272
Membrane Contactor Method 272
Supercritical Fluid Method 273
Hot Melt Extrusion Method 273
3.1.3 Application of SLNs in Drug Delivery 273
SLNs for Improved Oral Drug Delivery 273
SLNs for Oral Delivery of Proteins and Peptides 274
SLNs in Topical Delivery 274
SLNs in Pulmonary Delivery 274
SLNs in Ophthalmic Delivery 275
SLNs in Parenteral Delivery 275
SLNs for Targeted Delivery 275
3.2 Nanostructured Lipid Carriers 275
3.2.1 Production Techniques 276
3.2.2 Classification of NLC 276
Type I or Imperfect Type NLC 276
Type II or Amorphous Type NLC 277
Type III or Multiple (O/F/W) Type NLC 277
3.2.3 Applications of NLC in Drug Delivery 277
3.3 Lipid Polymer Hybrid Nanoparticles 277
3.3.1 Preparation Methods 279
Single- and Two-Step Approach 279
Modified Methods 279
3.3.2 Role in Drug Delivery 280
Drug Delivery in Cancer 280
Combination Therapy 280
Gene Delivery 280
Targeted Delivery 280
4 Lipid Vesicles 281
4.1 Liposomes 281
4.1.1 Classification of Liposomes 281
4.1.2 Liposome Preparation Methods 282
Mechanical Methods 282
Film Hydration Method 282
Methods Based on Solvent Removal 282
Reverse-Phase Evaporation 282
Ethanol Injection Method 283
Ether Injection Method 283
Size Transformation Methods 283
Freezing and Thawing 283
French Press Extrusion 283
Dehydration/Rehydration Method 283
Detergent Removal Method 284
4.1.3 Drug Loading 284
4.1.4 Applications of Liposome in Drug Delivery 284
4.2 Lipoplexes 286
4.2.1 Mechanism of Drug Delivery 286
4.2.2 Applications of Lipoplexes in Drug Delivery 287
4.3 Phytosomes 287
4.3.1 Method of Preparation 288
4.3.2 Applications of Phytosomes 289
Enhanced Biological Activity of Phytoconstituents or Extracts 289
4.3.3 Studies in Clinical Trials Using Phytosome Delivery 290
5 Characterization of Lipid Carriers 290
6 Storage Stability of Lipid Carriers 290
7 Conclusion 291
References 291
9 Nanocrystals for Delivery of Therapeutic Agents 300
Abstract 300
1 Introduction 301
2 Advantages of Nanocrystals 302
3 Formulation 304
3.1 Bottom-Up Approaches 304
3.2 Top-Down Approaches 306
3.2.1 Media Milling 306
3.2.2 High Pressure Homogenisation 306
3.3 Combination Methods 307
3.3.1 Teniposide Nanosuspension Drug Delivery System (TEN-NSDDS) 307
3.3.2 ARTcrystal® Technology 307
3.3.3 Combination Technology 309
3.3.4 H42/69/96 Technologies 309
3.3.5 Nanoedge® Technology 310
4 Stabilization 310
4.1 Selection Criteria for Stabilizers 311
4.1.1 Drug-Related Parameters 311
4.1.2 Stabilizer-Related Parameters 312
4.1.3 Dispersion Medium-Related Parameters 312
5 Characterization and Evaluation 312
6 Biopharmaceutical Aspects 313
7 Applications 315
7.1 Cancer Chemotherapy 315
7.2 Targeted Drug Delivery 315
7.3 Theranostic Applications 316
7.4 Safety and Efficacy 317
8 Market Status 319
9 Concluding Remarks 319
References 321
10 Inorganic Nanocomposites—A New Paradigm in Drug Delivery 326
Abstract 326
1 Introduction 327
2 Advantages of Inorganic Nanocomposites 328
3 Different Classes of Inorganic Nanocomposites 329
4 Applications of Inorganic Nanocomposites 329
5 Mesoporous Silica 331
5.1 Types of Mesoporous Silica 331
5.2 Synthesis of Mesoporous Silica 333
5.3 Methods of Drug Loading 334
5.3.1 Using Organic Solvent 334
5.3.2 Without Using Organic Solvent 335
Melt Method 335
Co-grinding Method 335
5.3.3 Loading with Supercritical Fluid Technology 335
5.4 Factors Influencing Drug Release from the Mesoporous Carrier 336
5.4.1 Effect of the Pore Size and Pore Volume 336
5.4.2 Effect of Surface Area and Surface Chemistry 336
5.4.3 Effect of Solvent 337
5.5 Application of Mesoporous Silica 337
5.5.1 Mesoporous Drug Delivery System for Enhanced Dissolution 340
5.5.2 Functionalized Mesoporous System 340
5.6 Mesoporous Silica Nanoparticles 340
5.6.1 Application of MSNs 341
Drug, Protein, and Gene Delivery 341
Stimuli Responsive Drug Delivery System 345
Targeted Drug Delivery System 346
5.6.2 Biocompatibility Issues of Mesoporous Material 346
6 Quantum Dots 347
6.1 General Procedure of Preparation of QD 348
6.2 Biocompatibility of QDs 350
6.3 Applications of QDs 351
7 Metal Oxides 351
7.1 Iron Oxide Nanoparticles 352
7.2 Preparation Method 353
7.3 Biocompatibility and Toxicity 353
8 Market and Clinical Status 356
9 Conclusion 357
References 358
11 Green Synthesized Gold Nanoparticles for Future Biomedical Applications 367
Abstract 367
1 Introduction 368
2 Gold Nanoparticles (AuNPs) History 369
3 Synthesis Strategies of AuNPs 369
3.1 Chemical Approach 370
3.2 Physical Approach 370
3.3 Biological Approach 371
4 Size, Shape and In Vitro Stability Studies 371
5 Biomedical Applications of Biologically Synthesized AuNPs 372
5.1 Biomedical Imaging and Cancer Diagnostics of b-AuNPs 374
5.2 Drug Delivery 376
5.3 Targeted Drug Delivery 379
5.4 Anticancer Agents 380
5.5 Photothermal Therapy in Cancer 381
5.6 Angiogenesis 383
5.7 Antioxidants 385
5.8 Antidiabetic Agents 385
5.9 Antibacterial, Antibiofilm, and Antifungal Activity 386
6 Toxicity, Biodistribution and Cellular Internalization of b-AuNPs 388
6.1 In Vitro Cytotoxicity 388
6.2 In Vivo Toxicity and Biodistribution Studies 388
6.3 Cellular Internalization 389
7 Mechanism of Green Synthesis of AuNPs 390
8 Advantages and Disadvantages of Green Synthesis 391
8.1 Advantages 391
8.2 Disadvantages 392
9 Future Opportunities and Challenges 392
10 Conclusions 393
Acknowledgements 393
References 393
12 Cationic Polyelectrolyte Vectors in Gene Delivery 402
Abstract 402
1 Introduction 403
2 Polysaccharide-Based Vectors 405
2.1 Graft Polymers Based on Polysaccharides 405
2.2 Grafted Copolymers of Chitosan 406
2.3 Grafted Copolymers of Pullulan 410
2.4 Grafted Polymers of Other Polysaccharides 411
3 Redox Responsive Vectors 411
3.1 Biological Redox Environment 412
4 Preparation of Bioresponsive Polyplexes 414
5 Reduction Sensitive Polymers and Intracellular Gene Delivery 415
5.1 Bioreducible PEI Polymers 415
5.2 Bioreducible Poly(amido)amines (PAA) 416
5.3 Other Reduction Sensitive Polymeric System 418
6 Conclusion 419
References 420
13 Nanoparticulate Immunotherapy: An Intelligent Way to Tailor Make Our Defense System 425
Abstract 425
1 Introduction 426
2 Nanoparticle Based Immunosuppression 428
2.1 Autoimmune Disorder 428
2.1.1 Delivery of Anti-inflammatory Molecules 429
2.1.2 Delivery of Autoantigens 430
2.1.3 T Cell Targeting 430
2.2 Allergy 431
2.3 Allotransplantation 433
2.3.1 Calcineurin Inhibitor-Nanoparticle Conjugate 434
2.3.2 Rapamycin-Nanoparticle Conjugate 435
2.3.3 Mycophenolate Mofetil (MMF)-Nanoparticle Conjugate 435
2.3.4 Genetic Material-Nanoparticle Conjugate 435
3 Nanoparticle Based Immunostimulation 435
3.1 Cancer 435
3.1.1 Delivery of Epigenetic Modulator 437
3.1.2 Delivery of Vaccine 438
3.1.3 Delivery of Cytokines 438
3.1.4 Nanoparticle-Based Targeted Delivery to the Tumour Microenvironment (TME) 439
3.2 Acquired Immune Deficiency Syndrome (AIDS) 440
4 Conclusions 444
Acknowledgements 444
References 444