Nasal Drug Delivery: Formulations, Developments, Challenges, and Solutions

Description

This book addresses the recent trends and clinical research being reported in last 5 to 10 years in the field of nasal drug delivery systems. In recent years, interest in using nasal passage as drug absorption site has received increased attention from formulation scientists. Nasal passages, even though a small surface area of the body as compared to other absorption passage such as Gastrointestinal tract or skin,  show significant possibility for drug absorption at a quicker rate. There is also a possibility of delivering drugs to the brain using this passage and targeting drugs through the nasal passage. The book has 19 chapters addressing various aspects of nasal drug delivery systems such as an overview of anatomy and physiology of the nasal passage from a drug delivery point of view to global market opportunities for nasal drug delivery. In between, it addresses various aspects of nasal drug delivery. There are very few titles exclusively dedicated to nasal drug delivery, covering the formulation and developmental aspects, and addressing the challenges and solutions. The primary audiences for the book are graduate students in field of medicine, pharmacy and also various researchers who are working in the area of nasal drug delivery in addition to students who are specializing in field of medicine in ENT. This book provides comprehensive information on all the aspects related to the nasal drug delivery of various drug molecules. Preface Contents Contributors Chapter 1: An Overview of the Anatomy and Physiology of Nasal Passage from Drug Delivery Point of View 1 Introduction 1.1 Nasal Drug Delivery Systems [1] 1.1.1 Nasal Anatomy and Physiology 2 Physiology of the Nose 2.1 Airway 2.2 Olfaction 2.3 Effects on Speech 2.4 Air Conditioning 2.5 Reflex Functions 2.6 Common Factors 3 Nasal Airflow 4 Abnormal Nasal Physiology 5 Tests of Nasal Physiology 6 Factors Affecting Intranasal Delivery 7 Nasal Passage Targeting the CNS 8 Barriers to Drug Transport from Nose to Brain 8.1 Mucociliary Clearance 8.2 Physico-Chemical Properties of the Drugs 9 The Sensitivity of the Nasal Mucosa as a Limiting Factor 10 Impact of Delivery Instructions, Patient Compliance, and Body Position 11 Conclusion References Chapter 2: Pharmacological and Clinical Problems with Special Focus on Nasal Drug Delivery 1 What Is the Nasal Passageway? 2 What Is the Blood-Brain Barrier? 3 Properties of Nasal Passages 4 Current Relevance with COVID-19 5 Benefits of Utilizing the Nasal Passageway 6 Possible Barriers to the Utilization of the Nasal Passageway 7 Properties of an Effective Nasal Delivery Drug 8 Conclusion 9 Future Trends References Chapter 3: Drug Absorption via the Nasal Route: Opportunities and Challenges 1 Introduction 2 Challenges Associated with Absorption of Nasal Drug Delivery Systems 2.1 Barriers Against Mucosal Drug Absorption 2.2 Toxicity Associated with Intranasal Applications 3 Drug Absorption Enhancers as Opportunity for Improving Nasal Drug Delivery 3.1 Surfactants 3.1.1 Phospholipids 3.1.2 Bile Salts and Their Derivatives 3.1.3 Fatty Acids 3.1.4 Non-ionic Surfactants 3.1.5 Biosurfactants 3.1.6 Animal-Derived Surfactants 3.2 Enzyme Inhibitors 3.3 Cationic Polymers 3.4 Polyamines 3.5 Tight Junction Modulators 4 Conclusion References Chapter 4: Factors Affecting the Design of Nasal Drug Delivery System 1 Introduction 2 Factors Related to Nasal Anatomy and Physiology 3 Factors Related to the Biologically Active Agent 4 Factors Related to the Formulation 4.1 Strategies and Technologies 4.1.1 Permeation Enhancers 4.1.2 Protein Inhibitors (Enzyme and Glycoprotein) 4.1.3 Nanostructured Systems 4.1.4 Mucoadhesive and Mucus-Penetrating Formulations 4.1.5 Other Strategies 5 Design and Optimization 6 Concluding Remarks References Chapter 5: Challenges in Targeting Nasal Passage and Nose-to-Brain Delivery via Nanoemulsions 1 Introduction 2 Composition of Nanoemulsion for Nasal Administration 2.1 Surfactants 2.2 Co-surfactant 2.3 Oil 3 Factors that Influence Nanoemulsion Transport from Nose to Brain 3.1 Globule Size 3.2 Zeta Potential 4 Methods of Preparation of Nanoemulsion 5 Intranasal Delivery of Nanoemulsion for CNS Disorders 5.1 Nanoemulsion in the Treatment of Alzheimer’s Disease 5.2 Nanoemulsion in the Treatment of Parkinson’s Disease 5.3 Nanoemulsion in the Treatment of Migraine 5.4 Nanoemulsion in the Treatment of Psychosis 5.5 Nanoemulsion in the Treatment of Epilepsy 6 Recent Patents on Nose-to-Brain Delivery for CNS Disorders 7 Current Challenges and Future Prospective for Intranasal Nanoemulsion 8 Conclusion and Future Prospective References Chapter 6: Potential Targeting Sites to the Brain Through Nasal Passage 1 Introduction 2 Drug Delivery Pathways 2.1 The Nasal Cavity 2.2 The Respiratory Region and Epithelium 2.3 The Olfactory Region and Epithelium 2.3.1 Olfactory Sensory Neurons 3 Drug Delivery Pathways/Brain Targeting Sites via the Intranasal Route 3.1 The Olfactory Pathway 3.2 The Trigeminal Pathway 3.3 The Lymphatic Pathway 3.4 The Systemic Pathway 4 Factors Affecting Nasal Absorption 5 Conclusion References Chapter 7: Biomedical Applications of Nanocarriers in Nasal Delivery 1 Introduction 2 Types of Nanocarriers 2.1 Polymeric Nanocarriers 2.2 Lipidic Nanocarriers 2.3 Metallic Nanocarriers 3 Characterization of Nanocarriers for Nasal Delivery 4 Biomedical Applications of Nanocarrier in Nasal Delivery 4.1 Targeted Delivery 4.2 Gene Therapy 4.3 Vaccine Delivery 4.4 Theranostic Application 4.5 Diagnostics Application 5 Conclusions and Future Perspectives References Chapter 8: Delivery of Vaccines via the Nasal Route 1 Introduction 2 Mucosal Delivery of Vaccines 3 Nasal Route 3.1 Anatomy of the Nose 3.2 Physiology of the Nose 4 The Mucosal Immune System 5 Nasopharyngeal-Associated Lymphoid Tissue (NALT) 6 Drug Uptake in the Nose 7 Absorption Through Nasal Route 7.1 Nasal Physiological Factors 7.1.1 Blood Flow 7.1.2 Mucociliary Clearance 7.1.3 Degradation and Excretion of Nasally Administered Drugs 7.2 Physicochemical Properties of Drugs 7.2.1 Lipophilicity/Hydrophilicity, Molecular Weight, and Degree of Ionization 7.2.2 Solubility 8 Types of Nasal Vaccines 8.1 Liposomes 8.2 Microspheres 8.3 Nanoparticles 9 Challenges with Nasal Vaccines 10 Conclusion References Chapter 9: An Overview on Nanocarriers for Nasal Delivery 1 Introduction 2 Key Anatomical Regions and Functions of Nasal Cavity 3 Nasal Delivery: Rationale and Design 4 Applications of Nasal Delivery 4.1 Vaccine Delivery 4.2 Topical/Local Delivery 4.3 Systemic Delivery 4.4 Nose-to-Brain Delivery 4.4.1 Nasal Transport Mechanisms from Nose-to-Brain 5 Nanocarriers for Nasal Delivery 5.1 Liposomes 5.2 Solid Lipid Nanoparticles (SLNs) 5.3 Nanoemulsions 5.4 Nanogels 5.5 Polymeric Nanoparticles 5.6 Polymeric Nanomicelles 5.7 Nanofibers 5.8 Dendrimers 6 Toxicity Concerns 7 Conclusion References Chapter 10: Nose-to-Brain Delivery of Peptides and Proteins 1 Introduction 2 Brain Drug Delivery 3 Barriers to Nose-to-Brain Drug Delivery 4 Nasal Route 4.1 Mucociliary Clearance 4.2 Transporter and Efflux System 4.3 Enzymatic Degradation 5 Pathways for the Intranasal (IN) Drug Delivery 6 Systemic Pathways 7 Mechanism of Drug Absorption Via Nose 7.1 Paracellular Route of Transport 7.2 Transcellular Route of Transport 8 Advantages and Disadvantages of IN Drug Delivery 9 Factors Influencing Nasal Drug Absorption 9.1 Factors Related to Drugs 9.1.1 Solubility and Dissolution Rate 9.1.2 Lipophilicity 9.1.3 Molecular Weight 9.1.4 Partition Coefficient and pKa 9.2 Factors Related to Formulation 9.2.1 pH and Mucosal Irritancy 9.2.2 Osmolarity 9.2.3 Viscosity 9.2.4 Dosage Form of the Formulation 9.3 Nasal Effect 9.3.1 Membrane Permeability 9.3.2 Environmental pH 9.3.3 Mucociliary Clearance 9.3.4 Cold and Rhinitis 10 Protein/Peptide Drug Delivery: Nose-to-Brain 10.1 The Importance of Nanocarriers 10.2 Proteins and Peptides 10.2.1 Insulin 10.2.2 Albumin 10.2.3 Oxytocin 10.2.4 Leptin 11 Future Perspectives and Conclusion References Chapter 11: Novel Mucoadhesive Polymers for Nasal Drug Delivery 1 Introduction 2 Natural Mucoadhesive Polymers and Their Derivatives 2.1 Chitosan and Its Derivatives 2.2 Cellulose Derivatives 2.3 Starch and Its Derivatives 2.4 Xanthan Gum and Xanthan Thiomers 2.5 Gellan Gum and Its Derivatives 2.6 Pectins and Methylated Pectins 2.7 Alginates 2.8 Gelatin and Its Derivatives 3 Synthetic Mucoadhesive Polymers 3.1 Polyacrylates 3.2 Polycarbophils 3.3 Miscellaneous Synthetic Polymers 4 Mucoadhesive Copolymers 5 Mucoadhesive Polymer Blends 5.1 Physical Blends 5.2 Polyelectrolyte Complexes 5.3 Cross-Linked Polymers 6 Conclusion and Future Perspectives References Chapter 12: Novel Approaches in Nasal In Situ Gel Drug Delivery 1 Introduction 2 In Situ Nasal Gel 2.1 Temperature-Induced In Situ Gel System 2.2 pH-Triggered Systems 2.3 Ionic Gelation 3 Recent Approaches 4 Safety Aspects References Chapter 13: Nasal Delivery of High Molecular Weight Drugs: Recent Trends and Clinical Evidence 1 Introduction 2 High Molecular Weight Drugs 2.1 Insulin 2.2 Desmopressin 2.3 Salmon Calcitonin 2.4 Oxytocin 2.5 Glucagon 2.6 Human Growth Hormone 2.7 Teriparatide (Recombinant Human Parathyroid Hormone) 2.8 The Miscellaneous 3 Superiorities and Limitations of Nasal Administration for High Molecular Weight Drugs 3.1 Nasal Blood Flow 3.2 Enzymatic Activity 3.3 Mucociliary Clearance 3.4 Nasal Absorption 3.5 Physical Condition of Nose 4 Recent Trends in Nasal Delivery of High Molecular Weight Drugs 4.1 Particulate Drug Delivery Systems 4.1.1 Microparticulate Systems 4.1.2 Nanoparticulate Systems 4.2 Polymers 4.2.1 Mucoadhesive Systems 4.2.2 Thermosensitive Systems 4.3 Absorption Enhancers 4.4 Enzyme Inhibitors 4.5 The Miscellaneous 5 Clinical Evidence on Nasal Delivery of High Molecular Weight Drugs 6 Future Directions and Conclusion References Chapter 14: Niosomes-Based Drug Delivery in Targeting the Brain Tumors Via Nasal Delivery 1 Introduction 2 Nasal Drug Delivery Route 2.1 The Blood-Brain Barrier (BBB) and Targeted Drug Delivery to the Brain 2.2 Transmitting to the Brain Through Nasal Passages 2.2.1 Olfactory Pathway 2.2.2 Trigeminal Pathway 2.2.3 Lymphatic Pathway 2.2.4 Systemic Pathway 2.3 Advantages and Disadvantages of the Nasal Drug Delivery Route 2.4 Mechanism of Drug Absorption from the Nasal Route 2.5 Nasal Anatomy and Physiology of the Nose 2.6 Brain Targeting Through the Nasal Route 2.7 Drugs for Glioblastoma Treatment Administered Intranasally 3 Nanotechnology-Based Drug Delivery 3.1 Structure of Niosomes 3.2 Advantages and Disadvantages of Niosomes-Based Drug Delivery Systems 3.3 Formulation Components of Niosomes 3.3.1 Non-ionic Surfactants 3.3.2 Cholesterol 3.3.3 Charge Inducer Molecules 3.4 Types of Niosomes 3.4.1 Proniosomes 3.4.2 Ethosomes 3.4.3 Bola-Surfactant Niosomes 3.4.4 Aspasomes 3.5 Methods of Preparation 3.5.1 Thin-Film Hydration (TFH)/Handshaking Method (HSM) 3.5.2 The “Bubble” Method 3.5.3 Ether Injection Method (EIM) 3.5.4 Sonication Method 3.5.5 Reverse Phase Evaporation Method (REV) 3.5.6 Micro-Fluidization Method 3.5.7 Trans-Membrane pH Gradient (Inside Acidic) 3.5.8 Single-Pass Technique 3.5.9 Heating Method (HM) 3.5.10 Freeze and Thaw Method (FAT) 3.5.11 Microfluidic Hydrodynamic Focusing 3.5.12 Dehydration-Rehydration Method 3.5.13 Supercritical Carbon Dioxide Fluid Method (scCO2) 3.5.14 The Handjani-Vila Method 3.6 Characterization of Niosomes 3.6.1 Size, Morphology, and Size Distribution of Niosomes 3.6.2 Entrapment Efficiency 3.6.3 Charge on Niosomes and Zeta Potential 3.6.4 Number of Lamellae 3.6.5 Membrane Rigidity 3.6.6 In Vitro Release 3.6.7 Tissue Distribution/In Vivo Study 3.6.8 Stability Studies 3.7 Routes of Administration 3.7.1 Intravenous 3.7.2 Intramuscular 3.7.3 Dermal and Transdermal 3.7.4 Oral 3.7.5 Ocular 3.7.6 Pulmonary 3.7.7 Nasal Administration 3.8 Applications of Niosomes 3.8.1 Delivery of Proteins and Peptides 3.8.2 Delivery of Anticancer Drugs 3.8.3 Delivery of Vaccine and Antigen 3.8.4 Carrier for Hemoglobin 3.8.5 Treatment of HIV-AIDS 3.8.6 Management of Psoriasis 3.8.7 Treatment of Leishmaniasis 3.8.8 Diagnostic Imaging 3.8.9 Enhancement of Bioavailability 3.9 Targeted Drug Delivery 3.10 Brain Targeting 4 Summary References Chapter 15: Nanosuspension – A Novel Drug Delivery System via Nose-to-Brain Drug Delivery 1 Introduction 2 Nanosuspension 3 Nose-to-Brain Drug Delivery 4 Permeation Enhancer Techniques Through the Nasal Route of Drug Administration 5 Types of Polymers Used in the Formulation of Nanosuspensions 5.1 Chitosan 5.2 Gelatin 5.3 Sodium Alginate 5.4 Albumin 5.5 Tamarind 6 Characterization and Evaluation of Nanosuspensions for Nose-to-Brain Drug Delivery 6.1 Fourier-Transform Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC) 6.2 Particle Size Analysis, Zeta Potential, and Polydispersity Index 6.3 Scanning Electron Microscope (SEM) 6.4 Encapsulation Efficiency 6.5 Stability Testing 6.6 Testing Direct Nose-to-Brain Delivery 6.6.1 In Vivo Models 6.6.2 In Vitro Models 6.6.3 Ex Vivo Models 7 Different Drugs Used and Current Research 8 Clinical Trials Investigating the Nose-to-Brain Drug Delivery 9 Recent Clinical Trials of Nanosuspensions 10 Conclusion References Chapter 16: Nasal Delivery of Micro and Nano Encapsulated Drugs 1 Introduction 2 Polymers Used to Encapsulate Drugs 3 Chitosan 4 Chitosan Surface Modifications 4.1 Carboxymethyl Chitosan (CMC) 4.2 Glutamate Chitosan 4.3 Deoxycholate-Chitosan-Hydroxybutyl Nanoparticles 4.4 Thiolated Chitosan 4.5 Deacetylated Chitosan 5 Drug Encapsulation with Chitosan Derivatives 5.1 Risperidone 5.2 Quetiapine Fumarate 5.3 Selegiline 5.4 Rotigotine 5.5 Methotrexate 5.6 Bromocriptine 5.7 Tapentadol Hydrochloride 5.8 Estradiol 5.9 Midazolam 5.10 Catechin Hydrate 5.11 Fexofenadine 5.12 Astragalus Polysaccharides 6 Drug Encapsulation with a Lipid Polymer Hybrid 6.1 Terbutaline Sulphate 6.2 Simvastatin 6.3 Lorazepam 7 Vaccine Encapsulation with Chitosan Derivatives 8 Drug Encapsulation with Co-polymers 8.1 Eugenol 8.2 Ropinirole 8.3 Desvenlafaxine Succinate 9 Poly (Lactic-Co-Glycolic Acid): PLGA 10 PLGA Surface Modifications 10.1 Pegylation 10.2 Lactoferrin 10.3 Peptides 10.3.1 RVG29 10.3.2 Octa-Arginine 10.3.3 RGD Tripeptide 10.3.4 Lectins 10.4 Monoclonal Antibodies 11 Drug Encapsulation with PLGA Derivatives 11.1 Lamotrigine 11.2 Haloperidol 11.3 Oxcarbazepine 12 Other Polymers Used for Intranasal Delivery 12.1 Polycaprolactone Polymers 12.2 Cellulose Derivatives 12.3 Alginate Derivatives 13 Conclusion References Chapter 17: Different Strategies for Nose-to-Brain Delivery of Small Molecules 1 Introduction 2 Mechanism of Nasal Absorption 3 Strategies for Improving Nasal Drug Delivery 3.1 Improve the Nasal Residential Time 3.2 Enhancing the Nasal Absorption 3.3 To Modify the Structure of the Drug to Change the Physicochemical Properties 4 Nose-to-Brain Delivery 5 Factors Relating to the Rate and Capacity of Drug Transport from Nose to Brain 5.1 Physicochemical Properties of the Drug 5.1.1 Relative Molecular Weight 5.1.2 Lipophilicity 5.1.3 Degree of Dissociation 5.2 Drug Concentration, Dosage, and Dosing Volume 5.3 Nasal Mucous Membrane Cilia Clearance and Dosage Form 6 Nanocarrier-Based Strategies Promoting Nose to Brain Delivery 6.1 Nanoparticles 6.1.1 Residence Time Increasing Nanoparticles 6.1.2 Lectin-Modified Nanoparticles 6.1.3 Lactoferrin-Modified Nanoparticles 6.1.4 Cell Penetrating Peptides-Modified Nanoparticles 6.2 Liposomes 6.2.1 Stealth Liposomes 6.2.2 Flexible Liposomes 6.2.3 Cell Penetrating Peptides Modified Liposomes 6.3 Exosome 6.3.1 Natural Bioactivities of Exosomes 6.3.2 Methodologies of Loading Drugs into Exosomes 6.3.3 Therapeutic Effects of Intranasally Administrated Exosomes 7 Nose to Brain Formulations 8 Future Prospective of Nose-to-Brain Delivery References Chapter 18: Is There a Global Market and Opportunities for Nasal Drug Delivery? Recent Trends in Global Nasal Delivery Market 1 Introduction 2 Current Products in Market 3 How the Growth of These Products Has Happened 4 Any New Technologies Introduced in Last Two Decades 5 Some Specific Diseases Where Nasal Drug Delivery is Most Applicable 6 Nanotechnology Applications in Nasal Drug Delivery 7 Forecasted Market Scenario for Nasal Drug Delivery 8 Conclusions References Chapter 19: Nasal Drug Delivery System: Regulatory Perspective 1 Introduction 2 The Global Regulatory Perspective Over Nasal Drug Delivery System 2.1 ICH 2.2 USFDA: United States Food and Drug Administration 2.3 European Medicines Agency 2.4 European Directorate for the Quality of Medicines & HealthCare 2.5 UK Medicines and Healthcare Products Regulatory Agency 2.6 Health Canada 2.7 The Standards Council of Canada 2.8 TGA Australia 2.9 Middle East/GCC 2.10 Indian Perspective 2.11 China’s Perspective 2.12 Nasal Vaccines and Regulations 2.13 Digital Medical Devices for Nasal Drug Delivery 3 Summary References Index