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