Pulmonary Drug Delivery Systems: Material and Technological Advances

Foreword
Preface
Contents
Contributors
About the Editors
1: Crystal Engineering: A Versatile Platform for Pulmonary Drug Delivery
	1.1	 Introduction
	1.2	 Crystal Engineering Techniques
	1.3	 Crystal Engineering and Pulmonary Drug Delivery
		1.3.1	 NanoCrySP—Novel Technology for Lung Delivery
		1.3.2	 AmphiCrys: Novel Crystal Engineering Platform
		1.3.3	 Drug–Drug Co-crystal for Respiratory Applications
		1.3.4	 Theophylline Crystal Engineering
		1.3.5	 Itraconazole Crystal Engineering
		1.3.6	 Budesonide Crystal Engineering
		1.3.7	 Dynamic Methods for Respirable Crystals
			1.3.7.1	 Plug Flow Crystallizer
			1.3.7.2	 Multiphase Static Mixer
			1.3.7.3	 Combined Crystallization Approach
			1.3.7.4	 Acidic Titration with Vertically Oriented Jet Mill
			1.3.7.5	 Slow Solvent Evaporation with Spray Drying
			1.3.7.6	 Crystal Designing with High Shear Agitator
			1.3.7.7	 Unidirectional Crystal Engineering
	1.4	 Future Perspective
	1.5	 Conclusion
	References
2: Thin-Film Freezing: A State-of-Art Technique for Pulmonary Drug Delivery
	2.1	 Introduction
	2.2	 Thin-Film Freezing for Pulmonary Drug Delivery
		2.2.1	 TFF Processed Inhalable Tacrolimus Particles
		2.2.2	 TFF Engineered Inhalable Voriconazole Particles
		2.2.3	 Respirable Remdesivir Particle Using TFF
		2.2.4	 Inhalable Monoclonal Antibodies Using TFF
		2.2.5	 TFF Routed Inhaled Powders
		2.2.6	 TFF Engineered Powders for Metered Dose Inhaler
	2.3	 Clinical Overview
		2.3.1	 Voriconazole Inhalation Powder
		2.3.2	 Tacrolimus Inhalation Powder
	2.4	 Future Perspective
	2.5	 Conclusion
	References
3: Supercritical Fluid Technology as a Tool for Improved Drug Delivery to the Lungs
	3.1	 Introduction
	3.2	 SCF-Based Manufacturing Technologies
		3.2.1	 Rapid Expansion of Supercritical Solutions (RESS) and Related Processes
		3.2.2	 Gas Anti-Solvent (GAS)
		3.2.3	 Aerosol Solvent Extraction System (ASES)
		3.2.4	 Solution-Enhanced Dispersion by Supercritical Fluids Process (SEDS)
		3.2.5	 Precipitation with Compressed Anti-Solvent (PCA)
		3.2.6	 Supercritical Anti-Solvent (SAS)
			3.2.6.1	 Temperature
			3.2.6.2	 Pressure
			3.2.6.3	 Nature of Solvent
			3.2.6.4	 Flow Rates and Nozzle Geometry
	3.3	 Properties of Powders Produced by SCF Techniques
		3.3.1	 Polymorphism
		3.3.2	 Particle Size
		3.3.3	 Stability
		3.3.4	 Commercial Application of SCF Technology
	3.4	 Conclusion
	References
4: Nano-in-Microparticles for Pulmonary Drug Delivery
	4.1	 Introduction
	4.2	 Types of Nanoparticle
		4.2.1	 Lipid-Based Nanoparticles
			4.2.1.1	 Lipid Nano-Emulsions
			4.2.1.2	 Liposomes
			4.2.1.3	 Lipid Nanoparticles
			4.2.1.4	 Solid Lipid Nanoparticles
			4.2.1.5	 Nanostructured Lipid Carriers
			4.2.1.6	 Lipid Nanocapsules
		4.2.2	 Polymeric Nanoparticles
			4.2.2.1	 Micelles
			4.2.2.2	 Polymersomes
			4.2.2.3	 Nanocapsules
			4.2.2.4	 Nanospheres
			4.2.2.5	 Dendrimers
			4.2.2.6	 Nanogels
		4.2.3	 Nanocrystals
		4.2.4	 Inorganic Nanoparticles
	4.3	 Inhalable Nanoparticles Frameworks
		4.3.1	 Nanoparticle-Microparticle Powder Systems (NPMPs)
		4.3.2	 Nanoparticle-Agglomerate Microparticles (NPAMs)
		4.3.3	 Nanoparticle-Embedded Microparticles
	4.4	 Approaches for Producing Inhalable Nanoparticles
		4.4.1	 Spray Drying
			4.4.1.1	 Nanoparticle-Microparticle Powder Systems
			4.4.1.2	 Nanoparticle-Agglomerate Microparticles (NPAMs)
				Nanosuspensions
				Polymeric Nanoparticles
				Lipid Nanoparticles
			4.4.1.3	 Nanoparticle-Embedded Microparticles (NPEMs)
				Nanosuspensions
				Polymeric Nanoparticles
				Lipid Nanoparticles
				Inorganic Nanoparticles
				Spray Freeze Drying
				Supercritical CO2-Assisted Spray Drying (SASD)
				Shelf Freeze Drying (FD) and Thin Film Freeze Drying (TFFD)
	4.5	 Conclusion
	References
5: Porous Particle Technology: Novel Approaches to Deep Lung Delivery
	5.1	 Introduction
	5.2	 Factors Affecting Inhaled Porous Particles Deposition
	5.3	 Preparation of Porous Particles in Lung Delivery
		5.3.1	 Method of Preparations
		5.3.2	 Double Emulsion Solvent Evaporation Production Method
		5.3.3	 Spray Drying Technology
		5.3.4	 PulmoSphere™
		5.3.5	 Supercritical Fluid-Anti-Solvent Technology
		5.3.6	 Spray Freeze Drying
		5.3.7	 Aerogel
		5.3.8	 Co-suspension Delivery Technology
	5.4	 Porous Particles in Metered Dose Inhaler
	5.5	 Application of Porous Particles in Pulmonary Drug Delivery
		5.5.1	 Local Treatment of Respiratory Diseases
		5.5.2	 Systemic Treatment Via Pulmonary Delivery
			5.5.2.1	 Thrombosis
			5.5.2.2	 Tuberculosis
			5.5.2.3	 Human Growth Hormone Deficiency and Luteinizing Hormone-Releasing Hormone
			5.5.2.4	 Cancer
			5.5.2.5	 Diabetes
		5.5.3	 Controlled Release
	5.6	 Summary
	References
6: Application of Numerical Simulation (CFD) to Probe Powder, Particles, and Inhalers
	6.1	 Introduction
	6.2	 Computational Fluid Dynamics
	6.3	 Particles Tracking
	6.4	 Application of Numerical Simulations
		6.4.1	 Simulation of the Airflow Field and Particle Motion Inside the Inhaler and Human Airways
		6.4.2	 Simulation of the Inter-Particle Forces and deagglomeration
		6.4.3	 Modeling of Advanced DPI Designs and Formulations
		6.4.4	 Modeling of Powder Deposition with Patient Factors
	6.5	 Future Trend of Numerical Simulations in Aerosol Delivery System Research
	6.6	 Summary
	References
7: Chitosan-Based Particulates Carriers for Pulmonary Drug Delivery
	7.1	 Introduction
	7.2	 Chitosan in Pulmonary Drug Delivery
		7.2.1	 Role of Chitosan in Carrier Engineering
		7.2.2	 Engineered Nicotine Particles for Pulmonary Delivery
		7.2.3	 Chitosan Particles for Pulmonary Delivery of Antibiotic Agents
		7.2.4	 Chitosan Functionalized Particles for Pulmonary Delivery of Biological Materials
		7.2.5	 Chitosan Decorated Microparticulate Systems
		7.2.6	 Chitosan-Coated Nanoparticulate Systems
		7.2.7	 Chitosan Containing Nebulized Particles
		7.2.8	 Chitosan-Based Carriers for Intranasal Delivery
		7.2.9	 Cancer Detection Assay
	7.3	 Future Viewpoint
	7.4	 Conclusion
	References
8: Multifunctional Cyclodextrins Carriers for Pulmonary Drug Delivery: Prospects and Potential
	8.1	 Introduction
	8.2	 Cyclodextrins in Pulmonary Drug Delivery
		8.2.1	 Cyclodextrins Functionalized Particles for Pulmonary Delivery of Biological Molecules
		8.2.2	 Engineered Cyclodextrin Particles for Pulmonary Delivery of Phytoconstituents
		8.2.3	 Respirable Cyclodextrin Antibiotics-Loaded Complex
		8.2.4	 Pulmonary Delivery of Anti-inflammatory Agent-Loaded Cyclodextrin Complex
		8.2.5	 Cyclodextrins Functionalized Nano-in-Micro Particles
		8.2.6	 Cyclodextrin Complex as Stability Enhancers
		8.2.7	 Cyclodextrin Engineered Nebulized Particles
	8.3	 Clinical Applications of Cyclodextrin Complex
		8.3.1	 CyPath Online: Biological Assay
		8.3.2	 Camptothecin Nanomaterials
	8.4	 Future Outlook
	8.5	 Conclusion
	References
9: TPGS Functionalized Carriers: An Emerging Approach for Pulmonary Drug Delivery
	9.1	 Introduction
	9.2	 TPGS in Pulmonary Drug Delivery
		9.2.1	 TPGS Functionalized Polymeric Micelles
		9.2.2	 TPGS Decorated Mixed Micelles
		9.2.3	 TPGS Decorated Liposomes
		9.2.4	 TPGS Functionalized Nanostructured Carriers
		9.2.5	 Spray Dried TPGS Particles for Pulmonary Delivery
		9.2.6	 TPGS Decorated Nebulized Particles
	9.3	 Future Outlook
	9.4	 Conclusion
	References
10: Engineering of Hydrogels for Pulmonary Drug Delivery: Opportunities and Challenges
	10.1	 Introduction
	10.2	 Pulmonary Delivery
		10.2.1	 Hydrogel Nano- and Micro-particles
		10.2.2	 Swellable Hydrogel Carriers
		10.2.3	 Enzyme Responsive Hydrogel Carriers
	10.3	 Nebulized Hydrogel Carriers
	10.4	 Hydrogel-Assisted Metered-Dose Inhalers
	10.5	 Clinical Applications of Hydrogels
		10.5.1	 Biologic Lung Volume Reduction System
		10.5.2	 Amiodarone Hydrogel
		10.5.3	 BioSentry
	10.6	Discussion
	10.7	 Conclusion
	References
11: Resourceful Quantum Dots for Pulmonary Drug Delivery: Facts, Frontiers, and Future
	11.1	 Introduction
	11.2	 Quantum Dots
	11.3	 QDs Synthesis Schemes
	11.4	 Pulmonary Applications of QDs
	11.5	 QDs Diagnostic Application
	11.6	 Future Viewpoint
	11.7	 Conclusion
	References
12: Metal-Organic Frameworks: A Toolbox for Multifunctional Pulmonary Applications
	12.1	 Introduction
	12.2	 Inhaled MOF Platforms
		12.2.1	 Engineered MOFs for Phytochemicals
		12.2.2	 Functionalized MOFs for Tuberculosis
		12.2.3	 Novel MOFs Platform for Anti-Inflammatory Agents
		12.2.4	 Nanostructured MOFs with Anticancer Potential
		12.2.5	 Surface Treated MOFs for Pulmonary Hypertension
		12.2.6	 MOF as Diagnostic Platform
	12.3	 Future Outlook
	12.4	 Conclusion
	References
13: Inhalable Prodrugs for Pulmonary Therapeutics
	13.1	 Introduction
	13.2	 Drug Metabolism in the Airways
	13.3	 Prodrugs Strategies for Pulmonary Therapy
		13.3.1	 Inhalable Platinum-Based Prodrugs
		13.3.2	 Inhalable Paclitaxel Prodrugs
		13.3.3	 Inhalable Camptothecin Prodrugs
		13.3.4	 Inhalable Doxorubicin Prodrugs
		13.3.5	 Inhalable Antibiotic Prodrugs
		13.3.6	 Prodrug Policy for Lung Cancer Treatment
		13.3.7	 Miscellaneous Inhalable Prodrugs
	13.4	 Clinical Outlook of Laninamivir Prodrug
	13.5	 Future Outlook
	13.6	 Conclusion
	References
14: Nucleic Acid Pulmonary Therapy: From Concept to Clinical Stance
	14.1	 Introduction
	14.2	 Nucleic Acid Types
		14.2.1	 Antisense Oligonucleotides (ASOs)
		14.2.2	 MicroRNAs (miRNAs)
		14.2.3	 Anti-microRNAs (Antagomirs)
		14.2.4	 Messenger RNAs (mRNAs)
		14.2.5	 Aptamers
		14.2.6	 Short Interfering RNAs (siRNAs)
	14.3	 The Pulmonary Route
		14.3.1	 Anatomy and Physiology of the Lungs
		14.3.2	 Particle Deposition Mechanisms
			14.3.2.1	 Inertial Impaction
			14.3.2.2	 Gravitational Sedimentation and Brownian Diffusion
			14.3.2.3	 Interception
			14.3.2.4	 Electrostatic Precipitation
		14.3.3	 Particle Clearance Mechanisms
	14.4	 Delivery Platforms
		14.4.1	 Devices
			14.4.1.1	 Nebulizers
			14.4.1.2	 Pressured Metered Dose Inhalers (pMDIs)
			14.4.1.3	 Dry Powder Inhalers (DPIs)
			14.4.1.4	 Soft Mist Inhalers (SMIs)
		14.4.2	 Formulation
			14.4.2.1	 Intrinsic Stabilizing Strategies
				Base Modifications
				Sugar-Phosphate Backbone Modifications
				Chemical Conjugation
			14.4.2.2	 Delivery Vectors
				Lipid-Based Nonviral Vectors
					Liposomes
					Solid Lipid Nanoparticles (SLN)
				Polymer-Based Nonviral Vectors
	14.5	 Current Outlook
	14.6	 Concluding Remarks
	References