Fundamentals of Pharmaceutical Nanoscience

Contents
About the Editors
Chapter 1: Introduction
	1.1 Pharmaceutical Nanoscience
	1.2 Pharmaceutical Innovation
	References
Part I: Nanomaterials Fabrication, Characterisation, and Use
	Chapter 2: Low-Molecular Weight Amphiphiles
		2.1 Introduction
		2.2 Molecular Architecture and Surface Activity
		2.3 Self-Assembly of Low-Molecular Weight Amphiphiles
			2.3.1 Thermodynamics of Self-Association
			2.3.2 Characterisation of Self-Assembled Structures
			2.3.3 Factors Affecting the Critical Micelle Concentration
				2.3.3.1 Surfactant Properties
				2.3.3.2 Solution Properties and Temperature
		2.4 Applications in Pharmaceutical Nanoscience
			2.4.1 Synthetic Surfactants
				2.4.1.1 Non-ionic Surfactants
				2.4.1.2 Ionic Surfactants
			2.4.2 Bile Salts
				2.4.2.1 Pharmaceutical Applications
			2.4.3 Self-Assembling Peptides
				2.4.3.1 Surfactant-Like Peptides
				2.4.3.2 Peptide Amphiphiles
		2.5 Conclusions
		References
	Chapter 3: Niosomes
		3.1 Introduction
		3.2 Niosomal Components
			3.2.1 Surfactants
			3.2.2 Cholesterol
			3.2.3 Charged Molecules
		3.3 Factors Governing the Niosome Formation
			3.3.1 Thermodynamic Features
			3.3.2 Hydrophile-Lipophile Balance
			3.3.3 Geometric Features of Amphiphilic Molecule
		3.4 Niosome Preparation
			3.4.1 Proniosome
			3.4.2 Heating Method (HM)
			3.4.3 Supercritical Carbon Dioxide Fluid (scCO2)
			3.4.4 Membrane Contactor
			3.4.5 Ball Milling Method
			3.4.6 Microfluidic Hydrodynamic Focusing
			3.4.7 Vesicle Purification
				3.4.7.1 Dialysis
				3.4.7.2 Gel Filtration
				3.4.7.3 Centrifugation/Ultracentrifugation
		3.5 Niosome Characterization
			3.5.1 Vesicle Size
			3.5.2 Zeta Potential and Surface Properties
			3.5.3 Bilayer Characterization
			3.5.4 Vesicle Stability
			3.5.5 Entrapment Efficiency
			3.5.6 In Vitro Release
			3.5.7 pH Sensitivity Assessment
		3.6 Niosome Applications
			3.6.1 Oral Delivery
			3.6.2 Intravenous Delivery
			3.6.3 Ocular Delivery
			3.6.4 Dermal and Transdermal Delivery
			3.6.5 Pulmonary Delivery
			3.6.6 Nose-to-Brain Delivery
			3.6.7 Anti-neoplastic Therapy
			3.6.8 Drug Targeting
				3.6.8.1 The Reticulo-Endothelial System (RES)
				3.6.8.2 Organs Other Than RES
			3.6.9 Immunological Applications
			3.6.10 Gene Delivery
			3.6.11 Diagnostic Agents
			3.6.12 Theranostic Agents
			3.6.13 Essential Oils Delivery
			3.6.14 Multifunctional Niosomes
		3.7 Final Considerations
		References
	Chapter 4: Solid Drug Nanoparticles
		4.1 Introduction and Brief Historical Perspective
			4.1.1 Advantages of SDNs: Drug Loading
			4.1.2 Advantages of SDNs: Drug Dissolution Kinetics
			4.1.3 Advantages of SDNs: Administration Routes
		4.2 Production of Solid Drug Nanoparticles
			4.2.1 Top-Down Methods for SDN Production
			4.2.2 Bottom-Up Methods for SDN Production
		4.3 Complexities of SDN Production
			4.3.1 The Need for Stabilisation
			4.3.2 Choice of Stabilisers and Excipients for SDN Manufacture
			4.3.3 Choice of Solvents if Required
			4.3.4 Translation to Clinical Scale
		4.4 Applications of Solid Drug Nanoparticles
			4.4.1 SDNs in Orally Dosed Medicines
			4.4.2 Parenteral Administration of SDNs
				4.4.2.1 Intravenous Injectables
				4.4.2.2 Subcutaneous and Intramuscular Injectables
				4.4.2.3 Inhalable Administration
				4.4.2.4 Topical Administration
				4.4.2.5 Ocular Delivery
		4.5 Conclusions
		References
	Chapter 5: Lipid Nanocapsules: Latest Advances and Applications
		5.1 Introduction
		5.2 Latest Advances and Applications in Oily Core LNCs
		5.3 Latest Advances and Applications in Reverse Micelle-Loaded LNCs
		5.4 Latest Advances and Applications in LNC-Based Hydrogels
		5.5 Latest Advances and Applications in Alternative Formulation Strategies with LNCs: LNCs as a Cargo
		5.6 Conclusion
		References
	Chapter 6: Polymer-Drug Conjugates
		6.1 Materials Chemistry
			6.1.1 Definition of Polymer-Drug Conjugates and General Background to This Technology
			6.1.2 Composition of a Polymer-Drug Conjugate
		6.2 Polymer-Drug Conjugate Synthesis
			6.2.1 Synthetic Strategies
			6.2.2 Purification
		6.3 Polymer-Drug Conjugate Characterisation
			6.3.1 Characterisation Parameters
			6.3.2 Techniques Employed to Characterise Conjugates
				6.3.2.1 Thin Layer Chromatography (TLC)
				6.3.2.2 UV-Vis Spectroscopy
				6.3.2.3 Nuclear Magnetic Resonance (NMR) Spectroscopy
				6.3.2.4 Infrared Spectroscopy (IR)
				6.3.2.5 High-Performance Liquid Chromatography (HPLC)
				6.3.2.6 Matrix-Assisted Laser Desorption/Ionisation Time of Flight (MALDI-TOF)
				6.3.2.7 Gel Permeation Chromatography (GPC)
				6.3.2.8 Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA)
				6.3.2.9 Asymmetric Field Flow Fractionation (FFF; AF4)
				6.3.2.10 Small Angle Neutron Scattering (SANS) and Small Angle X-Ray Scattering (SAXS)
		6.4 Application of Polymer-Drug Conjugates
			6.4.1 Treatment of Cancer
			6.4.2 Polymer-Drug Conjugates in Diseases Other than Cancer
				6.4.2.1 Inflammation
				6.4.2.2 Antimicrobial (Antibacterial, Antifungal, Antiviral, Antiprotozoal)
				6.4.2.3 Cardiovascular Diseases
				6.4.2.4 Central Nervous System
			6.4.3 Combination Therapy
			6.4.4 Current Status of Polymer-Drug Conjugates
		6.5 Conclusions
		Problems
		References
	Chapter 7: Polymeric Nanoparticles
		7.1 Introduction
		7.2 Materials Chemistry
		7.3 Preparation and Characterisation of Polymeric Nanoparticles
			7.3.1 Preparation of Polymeric Nanoparticles
			7.3.2 Polymer and Nanoparticle Characterisation
		7.4 Application of Polymer Nanoparticles in Pharmacy and Medicine
			7.4.1 Intravenous
				7.4.1.1 Anti-Cancer Drugs
				7.4.1.2 Anti-Infectives
			7.4.2 Oral
			7.4.3 Topical Ocular
			7.4.4 Brain Delivery
				7.4.4.1 Intravenous
				7.4.4.2 Nose to Brain
			7.4.5 Nasal
				7.4.5.1 Systemic Nasal Delivery
				7.4.5.2 Delivering to the Nasal Passages
			7.4.6 Subcutaneous
		7.5 Conclusion
		Problems
		References
	Chapter 8: Porous Si-Based Nanosystems for Immunotherapy Applications
		8.1 Immunotherapy
		8.2 Porous Silicon Nanoparticles (PSiNPs)
			8.2.1 PSiNPs-Based Immunotherapy
			8.2.2 Immunogenic Study of the PSiNP-Based Nanomaterials
			8.2.3 Applications of PSiNPs-Based Immunotherapy Platforms
		8.3 Porous Silica NPs
			8.3.1 Porous Silica NP-Based Immunotherapy
		8.4 Conclusions
		References
	Chapter 9: Ultrasmall-in-Nano
		9.1 Introduction
		9.2 The Need for Excretion
		9.3 Size-Dependent Properties of Nanoparticles
			9.3.1 Effect on Opsonization
			9.3.2 Effect on Cellular Internalization
			9.3.3 Effect on Renal Clearance
			9.3.4 Effect on Biodistribution
			9.3.5 Effect on Tumour Accumulation
			9.3.6 Effect on Toxicity
			9.3.7 Effect on Optical Properties
		9.4 Methods to Synthesize Ultrasmall AuNPs
		9.5 Approaches to Clustering
			9.5.1 Small Molecule Crosslinking
			9.5.2 Coating of Liposomes
			9.5.3 DNA Assembly
			9.5.4 Encapsulation/Ionic Interaction
		9.6 Accomplishments of Ultrasmall-in-Nano Constructs
		9.7 Conclusions and Future Perspectives
		References
Part II: Concepts Underpinning the Application of Biomedical Nanomaterials
	Chapter 10: Transmucosal Drug Delivery: Main Physiological Features and Modern Approaches
		10.1 Introduction
		10.2 Mucosal Routes of Drug Administration and Their Physiological Features
			10.2.1 Oral Cavity: Buccal, Gingival and Sublingual
			10.2.2 Gastrointestinal System: Oesophagus, Stomach, Intestine and Rectum
				10.2.2.1 Oesophageal Drug Delivery
				10.2.2.2 Stomach
				10.2.2.3 Small and Large Intestine
				10.2.2.4 Rectum
			10.2.3 Ocular Drug Delivery
			10.2.4 Respiratory System
				10.2.4.1 Pulmonary Drug Delivery
				10.2.4.2 Nasal Drug Delivery
			10.2.5 Genitourinary System: Vaginal and Intravesical
				10.2.5.1 Vaginal Drug Delivery
				10.2.5.2 Intravesical Drug Delivery
		10.3 Drug Delivery Approaches
			10.3.1 Mucoadhesive Dosage Forms
				10.3.1.1 Solids
					10.3.1.1.1 Tablets
					10.3.1.1.2 Suppositories
				10.3.1.2 Semi-solid Dosage Forms
					10.3.1.2.1 Gels
					10.3.1.2.2 Patches
				10.3.1.3 Liquid Dosage Forms
			10.3.2 First-Generation Mucoadhesives
			10.3.3 Second-Generation Mucoadhesives
			10.3.4 Mucus-Penetrating Nanoparticles
		10.4 Conclusion and Future Trends
		References
	Chapter 11: Nanomedicines for Delivery Across the Blood-Brain Barrier
		11.1 The Blood-Brain Barrier (BBB): Concept and Physiology
		11.2 Pathways for Transport Across the BBB
		11.3 Transcellular Permeation of Small Molecular Weight Drugs
		11.4 Pathways and Mechanism of Transport of Nanoparticulate Carriers Across the BBB
			11.4.1 Provoking a Transient Permeability Increase in the BBB Paracellular Pathway
			11.4.2 Passive Nanoparticulate Strategies for Brain Delivery
			11.4.3 Carrier-Mediated Transport for Brain Delivery
			11.4.4 Receptor-Mediated Transcytosis for Brain Delivery
			11.4.5 Adsorptive-Mediated Transcytosis for Brain Delivery
		11.5 Exosomes for Brain Delivery
		11.6 Particle Characteristics for Successful Brain and Brain Tumour Delivery: Pharmacokinetic and Pharmacodynamic Consideratio...
		11.7 Regulatory Considerations
		11.8 Conclusions
		Questions
		References
	Chapter 12: Non-deformable Nanoparticles and Transdermal Penetration
		12.1 Structure of Human Skin
		12.2 Permeation Pathways Through the Skin
		12.3 The Physicochemical Properties of a Permeant That Influence Skin Permeation and Fick´s Law of Diffusion
		12.4 Passive Permeation and Fick´s First Law of Diffusion
		12.5 Nanoparticles and the Skin
		12.6 The Penetration of Nanoparticles in Human Skin: A Theoretical Perspective
		12.7 Summary
		References
	Chapter 13: Nanotechnology and Hydrophobic Drug Solubilisation
		13.1 Introduction
			13.1.1 Drug Solubilisation
			13.1.2 Drug Partitioning
			13.1.3 Biopharmaceutics Classification Table
			13.1.4 Traditional Methods of Drug Solubilisation
		13.2 Nanotechnology for Hydrophobic Drug Solubilisation
		13.3 Routes of Delivery
		13.4 Drug Release from Nano-carriers
		13.5 Cellular Internalisation
		13.6 Biological Testing and Regulation
		13.7 Clinical Success
		13.8 Conclusion and Future Outlook
		References
	Chapter 14: Active Targeting of Nanomedicines
		14.1 Principles of Active Targeting of Nanomedicines
		14.2 Targeted Drug Delivery Processes
		14.3 Components of Active Targeting-Based Nanomedicines
			14.3.1 Nanocarriers
			14.3.2 Targeting Moieties
		14.4 Optimal Design of Actively Targeted Nanomedicines
		14.5 Examples of Active Targeting Nanomedicines
			14.5.1 Focus on Cancer-Active Targeting
				14.5.1.1 EPR Effect
				14.5.1.2 Cell Proliferation Targeting
				14.5.1.3 Angiogenesis-Related Targeting
			14.5.2 Actively Targeted Nanomedicines for Transport Across the Blood-Brain Barrier
			14.5.3 Actively Targeted Nanomedicines for Rheumatoid Arthritis
		14.6 Manufacturing Methods of Targeted Nanomedicines
			14.6.1 Conventional Manufacturing Methods: Bottom-up Versus Top-Down Approaches
			14.6.2 Novel Approaches in the Continuous Manufacturing of Targeted Nanomedicines: Microfluidic Chips
		14.7 Conclusions and Future Perspectives
		Problems
		References
Part III: Pharmaceutical Nanoscience Applications
	Chapter 15: Stimulus-Responsive Nanoparticles for Drug Delivery
		15.1 Introduction
		15.2 Nanoparticles That Are Responsive to Disease-Associated/Endogenous Stimuli
			15.2.1 Enzyme-Responsive Nanoparticles
			15.2.2 pH-Responsive Nanoparticles
			15.2.3 Glucose-Responsive Nanoparticles
			15.2.4 Redox-Responsive Nanoparticles
			15.2.5 Reactive Oxygen Species (ROS)-Responsive Nanoparticles
			15.2.6 Hypoxia-Responsive Nanoparticles
		15.3 Nanoparticles That Are Responsive to Externally Applied Stimuli
			15.3.1 Temperature-Responsive Nanoparticles
			15.3.2 Light-Responsive Nanoparticles
			15.3.3 Magnetic Field-Responsive Nanoparticles
			15.3.4 Ultrasound-Responsive Nanoparticles
		15.4 Conclusions
		References
	Chapter 16: Nanoparticles and Cancer Chemotherapy
		16.1 Introduction
		16.2 Cancer Chemotherapy
		16.3 Other Therapies for Cancer
		16.4 Nanotechnology and Chemotherapeutic Agents
		16.5 Challenges and Perspectives of Nanomedicines
		16.6 Concluding Remarks
		References
	Chapter 17: Anti-infective Drug Nanosystems
		17.1 Introduction
		17.2 Visceral Leishmaniasis
			17.2.1 Pathology
			17.2.2 Conventional Therapy
			17.2.3 Rationale of Using Nano-delivery System for Anti-leishmanial Drugs
		17.3 Systemic and Invasive Candidiasis
			17.3.1 Pathology
			17.3.2 Conventional Therapy
			17.3.3 Rationale of Using Nano-delivery System for Antifungal Drugs
		17.4 Microbial Keratitis
			17.4.1 Pathology
			17.4.2 Conventional Therapy
			17.4.3 Rationale of Using Nano-delivery Systems for Anti-infective Drugs in MK Treatment
		17.5 Tuberculosis
			17.5.1 Pathology
			17.5.2 Conventional Therapy
			17.5.3 Rationale of Using Nano-delivery Systems for Anti-TB Drugs
		17.6 Acquired Immunodeficiency Syndrome (AIDS)
			17.6.1 Pathology
			17.6.2 Conventional Therapy
			17.6.3 Rationale of Using Nano-delivery Systems for Anti-HIV Drugs
		17.7 Conclusion
		Questions
		References
	Chapter 18: Use of Nanotechnology in the Formulation of Vaccines
		18.1 Immunity and Vaccination
			18.1.1 Developing Immune Responses
			18.1.2 How Do Vaccines Promote Immune Responses?
		18.2 Current Vaccines Options
		18.3 Role of Nanotechnology in Vaccine Formulation
		18.4 Lipid Nanoparticle for the Delivery of Nucleic Acid Vaccines
		18.5 Nanoparticles as Adjuvants
			18.5.1 Liposomes, Niosomes and Other Vesicular-Based Adjuvants
			18.5.2 Virosomes
			18.5.3 Immune-Stimulating Complexes (ISCOMs) as Vaccine Adjuvants
			18.5.4 Polymeric Nanoparticles as Adjuvants
			18.5.5 Emulsion-Based Adjuvants
		18.6 Concluding Remarks
		References
	Chapter 19: Peptides, Proteins and Antibodies
		19.1 Peptide, Proteins and Antibodies as Novel Therapeutics and the Need for Novel Delivery Technologies
		19.2 Parenteral Peptide and Protein Delivery
			19.2.1 Polymeric Nanoparticles (PNPs)
			19.2.2 Lipid-Based Nanocarriers
			19.2.3 Peptide Nanofibres
			19.2.4 Protein Conjugates: PEGylation
			19.2.5 Protein Conjugates: Glycosylation
			19.2.6 Protein Conjugates: Albumin Conjugates
		19.3 Non-invasive Peptide Delivery
			19.3.1 Oral Peptide and Protein Delivery
			19.3.2 Nasal Peptide/Protein Delivery
			19.3.3 Pulmonary Peptide Delivery
		19.4 Future Perspectives and Conclusion
		Questions
		References
	Chapter 20: Nanosystems and Medical Imaging
		20.1 Introduction
		20.2 Nanoparticle Developments in Medical Imaging
			20.2.1 Active or Passive
			20.2.2 Big or Ultrasmall
			20.2.3 Monodisperse or Aggregated Nanoparticles
			20.2.4 Inert or Responsive
			20.2.5 Single Modal or Multi-modal
		20.3 Medical Imaging Modalities and Nanoparticle Imaging Agents
			20.3.1 Optical Imaging and Image-Guided Surgery
				20.3.1.1 NIR Nanoparticles and Optical Image-Guided Surgery
				20.3.1.2 Aggregation-Induced Emission (AIE)
				20.3.1.3 Cherenkov Imaging and Cherenkov Nanoparticle Agents
			20.3.2 Magnetic Resonance Imaging (MRI)
				20.3.2.1 Paramagnetic Contrast Agents
				20.3.2.2 Superparamagnetic Contrast Agents
				20.3.2.3 Magnetic Particle Imaging (MPI)
			20.3.3 Computed Tomography (CT) and Nuclear Imaging
				20.3.3.1 CT Imaging and Contrast Agents
				20.3.3.2 Nuclear Imaging and Contrast Agents
			20.3.4 Sound Wave-Based Imaging
				20.3.4.1 Ultrasound Imaging and Micro/Nano Bubbles
				20.3.4.2 Photoacoustic Imaging and Contrast Agents
		20.4 Clinical Translation Challenges of Nanoparticle Imaging Agents
			20.4.1 Clinically Approved Nanoparticle Imaging Agents
			20.4.2 Challenges for Clinical Translation
				20.4.2.1 Biocompatibility
				20.4.2.2 Target Organ Toxicity
				20.4.2.3 Immune Response
		20.5 Conclusion
		References
Index