Nanoscale Materials in Targeted Drug Delivery, Theragnosis and Tissue Regeneration (eBook)

Dr. Sudesh Kumar Yadav (DOB: 02-01-1976; POB: Bhiwani, Haryana) obtained his MSc in 1999 and PhD in 2002 from the Department of Biochemistry, CCS Haryana Agricultural University, Hisar. Subsequently, he worked as post-doctoral fellow at ICGEB, New Delhi (2002-2004). He joined CSIR-Institute of Himalayan Bioresource Technology, Palampur in 2004 and presently working there as principal scientist. Under his guidance, six students have obtained their PhD degrees. He has been working in the area of plant metabolic engineering and nanobiology.  In the plant metabolic engineering area, he has significantly contributed through his research towards understanding the caffeine metabolism in tea and reducing its caffeine levels through gene silencing. Also, flavonoid biosynthetic pathway genes from tea were explored in raising transgenic tobacco plants with improved flavonoid and antioxidants potential. His research work has provided the evidence to the production of low-seeded fruits through decreasing flavonols level by silencing of flavonol synthase. Currently, his focus is on understanding epigenetic regulation and role of small RNAs in the metabolic processes of plants. In nanobiology, his main work is on the exploration of plants for the synthesis of noble metallic nanoparticles and characterizing their phytochemicals involved therein. Such nanoparticles are very useful in various agricultural, medical and food applications. Secondly, he has been working towards improving the solubility, bioavailability and efficacy of important phytomolecules possessing activities like antioxidant, antimicrobial and anticancer.He has published more than 100 research articles in peer reviewed journals and 10 book chapters so far. For his outstanding research contributions in the area of plant sciences, he has been honoured with many prestigious awards; Indian National Science Academy (INSA)-Young Scientist Award-2008, The National Academy of Science, India (NASI)-Platinum Jubilee Young Scientist Award-2009, Council of Scientific and Industrial Research (CSIR)-Young Scientist Award-2010. He has been awarded BOYSCAST Fellowship during 2008 by DST, GOI for conducting advanced research at UCR, Riverside, USA for one year. He has been also selected “NAAS-Associate” by the National Academy of Agricultural Sciences from 2013 and conferred “Prof. Hira Lal Chakravarty Memorial Award” of Indian Science Congress Association (ISCA) for the year 2012-2013 during 100th Session of Indian Science Congress at Kolkata. Adding another feather to his achievements, he has now been selected by Haryana State Council for Science and Technology, Department of Science and Technology, Govt. of Haryana for the “Haryana Yuva Vigyan Ratna Award” 2011-12 for his excellent research contributions.  

Preface 5
Contents 7
About the Editor 12
Abbreviations 13
1 Nanoscale Materials in Targeted Drug Delivery 18
Abstract 18
1.1 Introduction 19
1.2 Approaches for Synthesis of Nanoscale Materials 20
1.3 Characterisation of Nanoscale Materials 21
1.4 Types of Nanoscale Materials 22
1.5 Targeted Drug Delivery 24
1.6 Various Nanoscale Materials in Drug Delivery 28
1.6.1 Polymeric Nanoparticles 28
1.6.2 Metallic Nanoparticles 28
1.6.3 Liposomes 28
1.6.4 Quantum Dots 28
1.6.5 Polymeric Micelles 29
1.6.6 Carbon Nanotubes 30
1.6.7 Dendrimers 30
1.6.8 Magnetic Nanoparticles 31
1.7 Conclusions 31
Acknowledgments 32
2 Biodegradable Nanoparticles and Their In Vivo Fate 37
Abstract 37
2.1 Introduction 38
2.2 Synthesis of Biodegradable Nanoparticles 40
2.2.1 Synthesis of PLGA and PLA Nanoparticles 40
2.2.2 Synthesis of Chitosan Nanoparticles 41
2.2.3 Synthesis of Protein Nanoparticles 41
2.3 Biodegradable Nanoparticles for Drug Delivery 42
2.3.1 Biodegradable Nanoparticles for Delivery of Anticancer Drugs 42
2.3.2 Biodegradable Nanoparticles for Delivery of Psychotic Drugs 44
2.3.3 Biodegradable Nanoparticles for Delivery of Antimicrobial Drugs 44
2.3.4 Biodegradable Nanoparticles for Delivery of Hepatoprotective Drugs 45
2.3.5 Biodegradable Nanoparticles for Proteins, Peptides and Nucleic Acids Delivery 45
2.4 Drug Release Mechanisms from Biodegradable Nanoparticles 45
2.5 Targeted Drug Delivery Using Biodegradable Nanoparticles 47
2.6 Biological Barriers Encountered by Biodegradable NPs 48
2.7 In Vivo Fate of Biodegradable Nanoparticles 49
2.8 Toxicity of Biodegradable Nanoparticles 50
2.9 Conclusions 51
Acknowledgments 51
References 51
3 Metallic Nanoparticles, Toxicity Issues and Applications in Medicine 56
Abstract 56
3.1 Introduction 57
3.2 Physico-Chemical Properties of Metal and Metal Oxide NPs 58
3.3 Synthesis of Metal and Metal Oxide NPs 59
3.3.1 Electrochemical Synthesis 60
3.3.2 Sonochemical Method 61
3.3.3 Thermal Decomposition 62
3.3.4 Laser Ablation 63
3.3.5 Chemical Reduction 64
3.3.6 Polyol Method 66
3.3.7 Microemulsion 66
3.3.8 Biological Synthesis 67
3.3.8.1 Bacteria-Mediated Synthesis 67
3.3.8.2 Fungus-Mediated Synthesis 68
3.3.8.3 Actinomycetes- and Yeast-Mediated Synthesis 68
3.3.8.4 Plant-Mediated Synthesis 69
3.4 Effect of Shape, Size and Surface Chemistry of NPs on Their Properties and Biological Behaviour 70
3.5 Medical Prospects of Metallic Nanoparticles 70
3.5.1 Disease Diagnostics 71
3.5.1.1 Imaging 71
3.5.1.2 Cancer Detection 72
3.5.2 Disease Therapy 74
3.5.2.1 Anti-microbial Activity 74
3.5.2.2 Cancer Treatment 75
3.5.2.3 Treatment of Other Diseases 77
3.5.2.4 Radiotherapy 78
3.5.2.5 Gene Therapy 79
3.5.2.6 Targeted Delivery and Controlled Drug Release 80
3.5.3 Tissue Engineering 81
3.5.4 Wound Healing and Skin Repair 82
3.5.5 Theranostics 83
3.6 Toxicity Issues Related to the Use of Nanomaterials 84
3.7 Conclusions 86
Acknowledgements 86
References 86
4 Liposomal and Phytosomal Formulations 96
Abstract 96
4.1 Introduction 97
4.2 Types of Liposomes 98
4.2.1 Liposomes Based on Drug Delivery Systems 98
4.2.2 Liposomes Based on Structural Parameters 99
4.3 Methods of Preparation of Liposomes 99
4.3.1 Passive Drug Loading/Encapsulation 100
4.3.1.1 Mechanical Method 100
4.3.1.2 Solvent Dispersion 101
4.3.1.3 Detergent Removal 102
4.3.2 Active Drug Loading/Encapsulation 103
4.4 Methods of Preparation of Phytosomes 103
4.4.1 Supercritical Fluids 103
4.4.2 Solvent Evaporation 103
4.4.3 Antisolvent Precipitation Technique 104
4.5 Mechanism of Liposome and Phytosome Formation 104
4.6 PhysicoChemical Characterisation of Liposomal and Phytosomal Formulations 104
4.7 Surface Modifications of Liposomes and Phytosomes 106
4.8 Targeting Mechanism of Liposomes and Phytosomes 106
4.8.1 Active Targeting 106
4.8.2 Passive Targeting 107
4.9 Medical Applications of Liposomes and Phytosomes 108
4.9.1 Diagnostics and Imaging 108
4.9.2 Drug Delivery 109
4.9.3 Tissue Regeneration 110
4.9.4 Antimicrobial Activity 112
4.10 Conclusions 112
Acknowledgments 112
References 113
5 Nanocellulose and Nanocomposites 118
Abstract 118
5.1 Introduction 119
5.2 Structure and Morphology of Cellulose 120
5.3 Sources of Cellulose 121
5.4 Types of Nanocellulose 121
5.4.1 Microfibrillated Cellulose (MFCs) 121
5.4.2 Cellulose Nanocrystals (CNCs) 123
5.4.3 Bacterial Nanocellulose (BNCs) 123
5.5 Preparation Methodologies of Nanocellulose 123
5.5.1 Pretreatment 123
5.5.1.1 Chemical Pretreatment 123
5.5.1.2 Enzymatic Pretreatment 124
5.5.2 Acid Hydrolysis 124
5.5.3 Mechanical Treatment 125
5.5.3.1 High-Pressure Homogenization 125
5.5.3.2 Grinding 125
5.5.3.3 Cryocrushing 125
5.5.3.4 Sonication 126
5.5.4 Combined Chemical and Mechanical Approach 126
5.6 Multiscale Characterizations 126
5.7 Physicochemical Properties 127
5.8 Factors Affecting Nanocellulose 128
5.9 Surface Chemical Modifications 129
5.9.1 Non-covalent Surface Modification 130
5.9.2 Silylation 130
5.9.3 Acetylation 130
5.9.4 Oxidation 131
5.9.5 Polymer Grafting 131
5.10 Nanocomposites Formation 131
5.11 Applications of Nanocellulose and Nanocomposites in Biomedical 132
5.11.1 Diagnostics 132
5.11.2 Drug Delivery 132
5.11.3 Tissue Engineering 134
5.11.4 Wound Repair 135
5.11.5 Antimicrobial Activity 135
5.12 Conclusions 136
Acknowledgements 136
References 136
6 Theragnosis: Nanoparticles as a Tool for Simultaneous Therapy and Diagnosis 141
Abstract 141
6.1 Introduction 142
6.2 Nanomaterials in Disease Diagnosis and Therapy 143
6.2.1 Metallic Nanoparticles 144
6.2.2 Quantum Dots 144
6.2.3 Silica NPs 145
6.2.4 Carbon Nanotubes 145
6.2.5 Dendrimers 146
6.2.6 Micelles 146
6.2.7 Liposomes 146
6.3 Different Imaging Modalities 147
6.3.1 Optical Imaging Systems 147
6.3.2 Magnetic Resonance Imaging (MRI) 148
6.3.3 Computed Tomography (CT) 148
6.3.4 Ultrasound (US) 149
6.3.5 Nuclear Imaging 149
6.4 Hybrid Imaging Modalities 150
6.4.1 Optical Imaging/MRI 150
6.4.2 MR-PET/SPECT 151
6.4.3 CT/MRI 151
6.4.4 PET/NIRF 152
6.4.5 SPECT/NIRF 152
6.5 Trimodal Imaging 152
6.5.1 CT/MR/Optical 153
6.5.2 PET/MR/Optical 153
6.5.3 SPECT/MR/Optical 153
6.6 Nanoparticles as Theragnostic Probes 153
6.6.1 Chemotherapy Via Theragnostic Nanotechnology 154
6.6.2 Photodyanamic Therapy 154
6.6.3 Photothermal Therapy 155
6.6.4 Hyperthermia Therapy 155
6.7 Factors Affecting Disease Diagnosis and Therapy 156
6.7.1 Biopersistence of NPs 156
6.7.2 Efficacy of NPs 156
6.7.3 Target Specificity of Theragnostic NPs 157
6.7.4 In Vivo Clearance of NPs 157
6.7.5 Nanotoxicity 158
6.8 Current Scenario and Future Aspects 158
6.9 Conclusion 160
Acknowledgments 160
References 160
7 Cellular Response of Therapeutic Nanoparticles 167
Abstract 167
7.1 Introduction 168
7.2 Pathways for Cellular Uptake of Nanoparticles 169
7.3 Monitoring Endocytic Pathways 170
7.4 Factors Affecting Cellular Response of Nanoparticles 171
7.5 Cellular Response of Therapeutic Nanoparticles 173
7.5.1 Metallic Nanoparticles 173
7.5.2 Silica Nanoparticles 174
7.5.3 Polymeric Nanoparticles 174
7.5.4 Quantum Dots 174
7.5.5 Liposomes 174
7.6 Protein Corona Formation on Therapeutic Nanoparticles 175
7.7 Characterisation of Protein Corona on Nanoparticles 176
7.7.1 Fourier Transform Infrared Spectroscopy (FTIR) 177
7.7.2 Raman Spectroscopy 177
7.7.3 Fluorescence Correlation Spectroscopy 177
7.7.4 Differential Centrifugal Sedimentation 177
7.7.5 Isothermal Titration Calorimetry 177
7.7.6 Liquid Chromatography-Mass Spectrometry 178
7.7.7 Matrix-Assisted Laser Desorption/Ionisation Time of Flight Mass Spectrometer (MALDI-TOF MS) 178
7.7.8 Electrophoresis 178
7.7.9 Size Exclusion Chromatography 179
7.7.10 Dynamic Light Scattering 179
7.7.11 Bioinformatic Tools 179
7.8 Properties of NPs Affecting Protein Corona Formation 179
7.9 Conclusions 181
Acknowledgments 181
References 181