Polymeric nanoparticles for the treatment of solid tumors

Preface
Contents
About the Editors
Chapter 1: The Tumor Microenvironment
1.1 Introduction
1.2 Abnormal Cellular Constituents of the Tumour Microenvironment
1.2.1 Pericytes
1.2.2 Endothelial Cells
1.2.3 Cancer-Associated Fibroblasts
1.2.4 Tumour-Associated Macrophages
1.2.5 Circulating Tumour Cells
1.2.6 Exosomes
1.2.7 Apoptotic Bodies
1.2.8 Circulating Tumour DNA
1.2.9 Inflammatory Mediators and Immune Cells
1.2.10 Adipose Tissue
1.2.11 Neuroendocrine System Involvement
1.2.12 Tumour Microenvironment Components
1.3 Abnormal Physiological Conditions of the Tumour Microenvironment
1.3.1 pH
1.3.2 Angiogenesis
1.3.2.1 Vascular Endothelial Growth Factor Family
1.3.2.2 Fibroblast Growth Factor and Fibroblasts
1.3.2.3 Notch Signalling Pathway
1.3.2.4 Transforming Growth Factor-β
1.3.3 Extracellular Matrix
1.3.4 Hypoxia
1.4 Conclusion
References
Chapter 2: Methods to Formulate Polymeric Nanoparticles
2.1 Introduction
2.2 Methods for Preparation of Polymeric Nanoparticle
2.2.1 Nanoprecipitation
2.2.2 Solvent Diffusion
2.2.3 Emulsification Solvent Evaporation
2.2.4 Interfacial Polymer Deposition
2.2.5 Salting Out
2.2.6 Supercritical Fluid Expansion
2.2.7 Complex Coacervation
2.2.8 Polymerization
2.2.9 Ionotropic Gelation
2.2.10 Spray Drying
2.2.11 Phase Separation Technique
2.3 Advanced Techniques for Preparation of Nanoparticles
2.3.1 Ring Opening Polymerization
2.3.2 Electro-Hydrodynamic Atomization
2.3.3 Desolvation of Macromolecules
2.3.4 Mussel-Inspired Chemistry for Polymerization
2.3.5 Self-Polymerization
2.4 Conclusion
References
Chapter 3: Natural Polymers-Based Nanoparticles Targeted to Solid Tumors
3.1 Introduction
3.2 Formulation and Characteristics of Natural Polymers
3.2.1 Polysaccharides
3.2.1.1 Chitosan
Formulation of Chitosan-Based Nanoparticles
3.2.1.2 Hyaluronic Acid
Formulations of Hyaluronic Acid-Based Nanoparticles
3.2.1.3 Alginates
Formulation of Alginate-Based Nanoparticles
3.2.1.4 Dextran
Formulation of Dextran-Based Nanoparticles
3.2.2 Protein-Based Polymers
3.2.2.1 Collagen
3.2.2.2 Gelatin
Formulation of Gelatin-Based Nanoparticles
3.2.2.3 Albumin
Formulation of Albumin-Based Nanoparticles
3.3 Application of Polymeric Nanoparticles in Targeting Solid Tumors
3.3.1 Active Targeting
3.3.2 Passive Targeting
3.4 Conclusion
References
Chapter 4: Optimization of Physicochemical Properties of Polymeric Nanoparticles for Targeting Solid Tumors
4.1 Introduction
4.2 Physiology of Solid Tumors
4.3 Physicochemical Properties of Polymeric Nanoparticles for Targeting Solid Tumors
4.3.1 Size and Molecular Weight
4.3.2 Hydrophobicity
4.3.3 Surface Charge
4.3.4 Crystallinity
4.3.5 Biocompatibility
4.4 Controlled Drug Release to Solid Tumors by Polymeric Nanoparticles
4.5 Polymeric Nanoparticles for Stimuli-Responsive Targeted Drug Delivery
4.6 Conclusion
References
Chapter 5: Passive and Active Targeting for Solid Tumors
5.1 Introduction
5.2 Targeting Methods
5.2.1 Passive Targeting
5.2.2 Active Targeting
5.2.2.1 Targeting of Cancer Cell
5.2.2.2 Targeting of the Tumoral Endothelium
5.2.2.3 Stimuli-Responsive Nanocarriers
Internal Stimuli
External Stimuli
5.3 Surface-Modified Targeted Nanoplatforms
5.3.1 Antibody, Enzymes and Proteins
5.3.2 Aptamers
5.3.3 Folate
5.3.4 Transferrin
5.3.5 Albumin
5.3.6 Biotin
5.3.7 Hyaluronic Acid
5.3.8 Toxins
5.3.9 Nucleic Acid
5.3.10 Virus
5.3.11 Affibodies
5.3.12 Peptides and Polypeptides
5.3.13 Miscellaneous
5.4 Challenges
5.4.1 Extravasation and the Enhanced Permeability and Retention Effect
5.4.2 Tumor Microenvironment and Tumor Interstitium
5.4.3 Physiological Barriers and pH
5.4.4 Efficacy Versus Toxicity
5.4.5 Translation from the In Vivo Model to the Human Model
5.4.6 Metastasis
5.4.7 Selection of Material for Designing Nanocarriers
5.5 Preclinical and Clinical Intervention for Transposing to Market
5.6 Commercialization and Government Regulations
5.7 Conclusion
References
Chapter 6: Polymeric Nanoparticles to Entrap Natural Drugs for Cancer Therapy
6.1 Introduction
6.2 Cancer
6.3 Drugs of Natural Origin in Cancer Chemotherapy
6.4 Role of Nanoparticles in Cancer Therapy
6.4.1 Concept and Recent Development of Polymeric Nanoparticles Conjugated with target-specific ligands
6.4.1.1 Active Targeting
6.4.1.2 Passive Targeting
6.4.1.3 Advances of Polymeric Nanoparticles in Conjugation with target-specific ligands
6.5 Polymeric Nanocarriers in Guided Cancer Therapy
6.6 Polymeric Nanoparticles Entrapping Drugs of Natural Origin
6.6.1 Polymers and Drugs of Natural Origin
6.6.1.1 Natural and Synthetic Polymers for the Preparation of Polymeric Nanoparticles
6.6.1.2 Drugs of Natural Origin for Polymeric Nanoparticles in Cancer Therapeutics
6.6.2 Mechanism of Drug Release for Polymeric Nanoparticles
6.6.2.1 Diffusion Through Water-Filled Pores
6.6.2.2 Diffusion Through the Polymeric Matrix
6.6.2.3 Osmotic Pumping
6.6.2.4 Erosion
6.6.3 Clinical Applicability
6.6.4 Recent Patents and Marketed Products Approved for Cancer Treatment
6.7 Regulatory Compliance
6.8 Perspective
6.9 Conclusion
References
Chapter 7: Polymeric Nanoparticles that Entrap Drug Combinations Targeted to Solid Tumors
7.1 Introduction
7.2 Types of Polymeric Nanoparticles
7.2.1 Chitosan
7.2.2 Gelatin
7.2.3 Polyethylene Glycol
7.2.4 Polyalkyl Cyanoacrylate
7.2.5 Polyesters
7.2.6 Polylactic Acid
7.2.7 Polyglycolide
7.2.8 Poly(Lactic-Co-Glycolic Acid)
7.2.9 Polycaprolactone
7.2.10 Polyvinyl Alcohol
7.3 Advantages of Combinational Therapy Versus Single Drug in Nanosystems
7.4 The Targeting Approach
7.4.1 Passive Targeting of Polymeric Nanoparticles Entrapping Combination of Drugs
7.4.2 Active Targeting of Polymeric Nanoparticles Entrapping Combination of Drugs
7.5 Conclusion
References
Chapter 8: Ligands Specific to Over-expressed Receptors in Solid Tumors
8.1 Introduction
8.2 Interventions for the Treatment of Solid Tumors
8.3 Ideal Anticancer Drug Formulation
8.4 Selective Targeting of Cancer Tissues
8.5 Active Targeting or Smart Targeting
8.6 Over-Expressed Receptors and Their Ligands in Solid Tumors
8.6.1 Epidermal Growth Factor Receptor
8.6.2 Folate Receptors
8.6.3 Fibroblast Growth Factor Receptors
8.6.4 Guanine Nucleotide Binding Protein Coupled Receptors
8.6.5 Integrin Receptor
8.6.6 Sigma Receptor
8.6.7 Transferrin Receptor
8.6.8 Vascular Endothelial Growth Factor Receptor
8.6.9 Other Receptors
8.7 Factors Affecting the Selection of Targeting Ligand
8.8 Drug Delivery Systems, Drug Carriers and Smart Vehicles
8.9 Conclusion
References
Chapter 9: Ligand Targeted Polymeric Nanoparticles for Cancer Chemotherapy
9.1 Introduction
9.2 Mechanism of Ligand Decorated Nanoparticles Uptake by the Cell
9.3 Ligand Directed Active Targeting for Cancer Treatment
9.3.1 Small Molecule Directed Active Targeting Polymeric Nanoparticles
9.3.1.1 Folic Acid
9.3.1.2 Biotin
9.3.1.3 Glycyrrhetinic Acid
9.3.2 Polysaccharide Directed Active Targeting Polymeric Nanoparticles
9.3.2.1 Galactosamine
9.3.2.2 Hyaluronic Acid
9.3.3 Proteins Directed Active Targeting Polymeric Nanoparticles
9.3.3.1 Transferrin
9.3.3.2 Lactoferrin
9.3.3.3 Epidermal Growth Factor
9.3.3.4 Lectin
9.3.3.5 Monoclonal Antibody
9.4 Conclusion
References
Chapter 10: Polymeric Nanoparticles as Theranostics for Targeting Solid Tumors
10.1 Introduction
10.2 Theranostic Polymeric Nanomedicine for the Treatment of Solid Tumor Cancer
10.2.1 Polymeric Gold Nanoparticles
10.2.2 Polymeric Micelles
10.2.3 Polymeric Superparamagnetic Nanoparticles
10.2.4 Quantum Dots-Loaded Polymeric Nanoparticles
10.2.5 Polymeric Nanoparticles Containing Dendrimers
10.2.6 Polymeric Nanoparticles Along with Carbon Nanotubes
10.2.7 Miscellaneous Carriers
10.2.7.1 Polymeric Liposomes
10.2.7.2 Polymersomes
10.3 Polymeric Nanoparticles in Clinical Trials
10.4 Conclusion
References
Chapter 11: Oral Delivery of Polymeric Nanoparticles for Solid Tumors
11.1 Introduction
11.2 Gastrointestinal Tract Physiology
11.3 Physiological Barriers as Hurdles for the Oral Delivery of Chemotherapeutics
11.3.1 Biochemical Barrier
11.3.2 Mucosal Barrier
11.3.3 Cellular Permeability Barrier
11.4 Biopolymeric Nano-Drug Delivery Systems for Oral Administration of Chemotherapeutics
11.4.1 Protein-Based Biopolymers
11.4.1.1 Gelatin
11.4.1.2 Collagen
11.4.2 Poly-Amino and Poly-Ester Based Biopolymers
11.4.2.1 Poly(Lactic-Co-Glycolic Acid)
11.4.2.2 Polyglutamic Acid
11.4.3 Polysaccharide-Based Biopolymers
11.4.3.1 Chitosan
11.4.3.2 Pullulan
11.4.3.3 Hyaluronic Acid
11.4.3.4 Alginates
11.5 Conclusion
References
Chapter 12: Polymeric Nanoparticles to Target Glioblastoma Tumors
12.1 Introduction
12.2 Glioblastoma
12.3 Advances in the Development of Novel Therapeutics for Glioblastoma
12.4 Drug Delivery to the Brain
12.5 Polymeric Nanoparticles for Targeting Glioblastoma
12.6 Peptide-Receptor as a Dual-Targeting Drug Delivery Approach
12.7 Dual-Targeting of Both Glioma and Neovascular Cells
12.8 Aptamer-Peptide Conjugates as a Dual-Targeting Delivery System
12.9 Routes of Administration of Nanoparticles in the Treatment of Malignant Gliomas
12.10 Challenges Related to Nanotherapy of Malignant Gliomas
12.10.1 Reticulo Endothelial System
12.10.2 Renal System
12.10.3 Blood Brain Barrier
12.10.4 Pathophysiological Barriers in Cancer
12.10.5 Multidrug Resistance
12.11 Conclusion
References
Chapter 13: Polymeric Nanoparticles to Target Lung Cancer
13.1 Introduction
13.1.1 Pathology of Lung Cancer
13.2 Modalities for the Treatment of Lung Cancer and Limitations
13.2.1 Photodynamic Therapy
13.2.2 Surgery
13.2.3 Chemotherapy
13.2.4 Radiation Therapy
13.3 Advances in Drug Delivery Systems for the Diagnosis of Lung Cancer
13.4 Polymer-Based Nanoparticulate System for the Management of Lung Cancer
13.4.1 Poly(Lactic-Co-Glycolic Acid) Based Nanoparticles
13.4.2 Polylactic Acid Based Nanoparticles
13.4.3 Cellulose Acetate Phthalate-Based Nanoparticles
13.4.4 Polycaprolactone-Based Nanoparticles
13.4.5 Hyaluronic Acid Nanoparticles
13.4.6 Other
13.5 Benefits of Drug Delivery Systems for the Management of Lung Cancer
13.6 Recent Patents and Clinical Trials on Drug Delivery Systems for Lung Cancer
13.7 Conclusion
References
Chapter 14: Polymer-Based Nanoplatforms for Targeting Breast Cancer
14.1 Introduction
14.1.1 Breast Cancer Types and Cellular Targets
14.1.2 Types of Polymeric Materials and Nanoplatforms
14.1.3 Current Trends
14.2 Strategies for Choosing Polymeric Nanomaterials
14.3 Polymeric Nanoplatforms for Cargo Delivery to Tumor Cells
14.3.1 Polymeric Nanoparticles
14.3.2 Polymer-Based Nanocomposites
14.3.3 Polymeric Nanoplexes
14.3.4 Surface-Modified Nanoplatforms
14.3.5 Antibodies and Immunological Agents
14.3.6 Aptamers
14.3.7 Small Interfering RNA and Messenger RNA
14.3.8 Miscellaneous
14.4 Polymeric Nanoparticles and Nanomaterials-Based Theranostic Strategies
14.5 Toxicological Perspectives of Polymeric Nanoplatforms
14.6 Conclusion
References
Chapter 15: pH-Sensitive Polymeric Nanoparticles for Cancer Treatment
15.1 Introduction
15.2 Mechanism of Action of pH-Sensitive Polymeric Nanoparticles
15.3 Designing of pH-Sensitive Polymeric Nanoparticles
15.3.1 Charge Shifting Polymers
15.3.2 Acid Labile Linkers as Pendant Functionality
15.3.3 Acid Linkers to Produce Cross-Linked Particles
15.4 Characteristics of Polymers Used for pH-Sensitive Polymeric Nanoparticles
15.5 Application of pH-Sensitive Polymeric Nanoparticles in the Treatment of Cancer
15.5.1 Change of Hydrophobic Property to Hydrophilic Property by Transfer of Charge
15.5.2 Change of Hydrophilic Property to Hydrophobic Property by Transfer of Charge
15.5.3 pH-Responsive Polymers with Acid Labile Linkages
15.5.4 Crosslinking
15.6 Conclusion
References
Chapter 16: Polymeric Nanoplatforms for the Targeted Treatment of Prostate Cancer
16.1 Introduction
16.2 The Emerging Era of Polymeric Nanoparticles
16.3 Surface Engineered Polymeric Nanoparticles for Prostate Cancer
16.3.1 Passive Targeting
16.3.2 Ligand-Based Targeting
16.4 Polymeric Nanoparticles for Targeting Prostate Cancer
16.4.1 Solid Dispersion of Polymeric Nanoparticles
16.4.2 Conjugated Polymeric Nanoparticles
16.4.3 Polymer-Lipid Hybrid Systems
16.4.4 Polymeric Micelles
16.4.5 Polyplexes
16.4.6 Miscellaneous Polymeric Nanoparticles
16.5 Stimuli-Responsive Polymeric Nanoparticles
16.5.1 pH-Responsive Polymeric Nanoparticles
16.5.2 Enzyme-Responsive Polymeric Nanoparticles
16.5.3 Ultrasound-Triggered Polymeric Nanoparticles
16.5.4 Dual-Responsive Polymeric Platforms
16.6 Advances in Polymeric Nanoparticles for Prostate Cancer
16.6.1 Polymer-Based Superparamagnetic Nanoparticles
16.6.2 Polymeric Nanoparticles Bearing Radionuclide,  Magnetic Resonance Imaging Agents and Metal Nanoparticles
16.6.3 Miscellaneous Advanced Polymeric Platform
16.7 Challenges
16.8 Conclusion
References
Chapter 17: Cellular Internalization and Toxicity of Polymeric Nanoparticles
17.1 Introduction
17.2 Factors Affecting Cellular Internalization of Polymeric Nanoparticles in Tumors
17.2.1 Particle Size
17.2.2 Particle Shape
17.2.3 Surface Charge
17.2.4 Conjugating Ligands
17.3 Toxicity of Nanoparticles
17.4 Conclusion
References
Chapter 18: Prospects and Challenges in the Treatment of Solid Tumors
18.1 Introduction
18.2 Current Treatment of Solid Tumors
18.2.1 Chemotherapy
18.2.2 Radiotherapy
18.2.2.1 Types of radiotherapy
18.2.3 Surgery
18.3 Advantages and Disadvantages of Treatments
18.3.1 Advantages
18.3.2 Disadvantages
18.4 Challenges
18.4.1 Immune Evasion Mechanisms in Tumors
18.4.2 Clinical Implementation of Next-Generation Sequencing Technologies
18.4.3 Conducting Biomarker-Driven Clinical Trials
18.4.4 Tumor Heterogeneity and Resistance
18.5 Perspective
18.5.1 Better Classification of Tumors
18.5.2 Simplification and Acceleration of the Drug Development System
18.5.3 Design of Trials
18.5.4 Role of Nano-Formulation
18.6 Conclusion
References
Index