Cover
Half Title
Title Page
Copyright Page
Contents
Preface
Part I: Fundamentals
1. Recent Trends in Nanotechnology for Brain Delivery: A Brief Outlook
2. Understanding Brain Delivery
2.1 The Central Nervous System in Drug Discovery and Development
2.2 CNS Barriers and Fluids
2.3 Efflux Transporters at the BBB
2.4 BBB Evolution in Physiological and Pathological States
2.5 Conclusions
3. Novel Routes to Accessing the Brain: Intranasal Administration
3.1 Introduction
3.2 Nose-to-Brain Drug Delivery
3.2.1 Pathways and Mechanisms of Nose-to-Brain Transport
3.3 Nose-to-Brain Delivery Assessment: Experimental Issues
3.3.1 Experimental Models
3.3.2 Study Design
3.3.3 Assessment Parameters
3.4 Nose-to-Brain Delivery of Central Drugs
3.5 Conclusions
Part II: Nanomedicines
4. Organic Nanocarriers for Brain Drug Delivery
4.1 Introduction
4.2 Pathways for Nanocarrier Administration to the Brain
4.2.1 Administration Routes
4.2.2 Transport Routes across the BBB
4.3 Self-Assembly Organic Nanocarriers for Brain Drug Delivery
4.4 Vesicles: Liposomes, Ethosomes and Polymersomes
4.4.1 Liposomes
4.4.1.1 Liposomes in Alzheimer's disease
4.4.1.2 Liposomes in Parkinson's disease
4.4.1.3 Liposomes in cerebral ischaemia/reperfusion
4.4.1.4 Liposomes in brain tumours
4.4.2 Ethosomes
4.4.3 Polymersomes
4.5 Micelles: Polymeric and Lipidic
4.6 Nanoparticles: Lipid Nanoparticles and Polymeric Nanoparticles
4.6.1 Lipid Nanoparticles
4.6.1.1 Solid lipid nanoparticles
4.6.1.2 Nanostructured lipid carriers
4.6.2 Polymeric Nanoparticles
4.7 Micro- and Nanoemulsions
4.8 Synthetic Organic Nanocarriers for Brain Drug Delivery
4.8.1 Dendrimers
4.9 Biodegradation/Bioelimination of Organic Nanocarriers from the Brain
4.10 Conclusions and Future Perspectives
5. Magnetic and Plasmonic Nanoparticles for Brain Drug Delivery
5.1 Introduction
5.2 Relevant Properties of Inorganic Nanoparticles for Brain Drug Delivery
5.2.1 Gold Nanoparticles
5.2.2 Magnetic Nanoparticles
5.3 Synthesis Procedures
5.3.1 Gold Nanoparticles
5.3.2 Magnetic Nanoparticles
5.4 Surface Modification Strategies towards Brain Delivery
5.5 Nanoparticles for Brain Delivery
5.5.1 Gold Nanoparticles
5.5.2 Magnetic Nanoparticles
5.6 Concluding Remarks
6. Hybrid Nanosystems
6.1 Introduction
6.2 Hybrid Nanosystems for Brain Cancer
6.3 Hybrid Nanosystems for Neurodegenerative Disorders
6.3.1 Hybrid Nanosystems for Alzheimer's Disease
6.3.2 Hybrid Nanosystems for Parkinson's Disease
6.4 Hybrid Nanosystems for Cerebral Ischaemia
6.5 Conclusions
7. Drug Nanocrystals
7.1 Introduction
7.2 Relevant Nanocrystal Physicochemical Properties
7.3 Preparation of Nanocrystals
7.3.1 Top-Down Techniques
7.3.1.1 Wet media milling
7.3.1.2 High-pressure homogenisation
7.3.2 Bottom-Up Techniques
7.3.2.1 Bottom-up: evaporation methods
7.3.2.2 Bottom-up: precipitation methods
7.3.3 Combination of Top-Down and Bottom-Up Techniques
7.4 Stability of Nanocrystals
7.4.1 Aggregation and Ostwald Ripening
7.4.2 Solid Forms: Polymorphs, Amorphous Phases and Solvates
7.5 Nanocrystals for Brain Drug Delivery
7.5.1 Oral Administration
7.5.2 Parenteral Administration
7.5.3 Nasal Administration
7.6 Concluding Remarks
8. Lipid Nanocarriers for Oligonucleotide Delivery to the Brain
8.1 Introduction
8.2 Oligonucleotide-Based Therapeutics
8.2.1 Antisense Oligonucleotides
8.2.2 RNA Interference
8.2.3 Anti-miRNA oligonucleotides
8.2.4 Aptamers
8.2.5 Antiproliferative Oligonucleotides
8.3 Lipid-Based Nanocarriers for Brain Delivery
8.3.1 Oligonucleotide-Lipid Conjugates
8.4 Vesicular Systems: Liposomes and Niosomes
8.5 Natural Vesicular Systems: Exosomes
8.6 Solid Lipid-Based Nanocarriers
8.7 Conclusions
9. Carriers for Nucleic Acid Delivery to the Brain
9.1 Introduction
9.2 Nonviral Nucleic Acid Carriers
9.3 Brain-Targeted Nucleic Acid Delivery
9.3.1 Transport across the Blood-Brain Barrier
9.3.1.1 Protein ligands
9.3.1.2 Peptide ligands
9.3.1.3 Carrier-mediated transport
9.3.2 Blood-Brain Barrier Disruption
9.3.3 Intracranial Delivery
9.4 Glioma-Targeted Nucleic Acid Delivery
9.5 Conclusions
10. Advances in Nanotheranostics with Plasmonic and Magnetic Nanoparticles
10.1 Nanomedicine in Brain Therapy
10.2 Nanotheranostics: Concepts and Strategies
10.2.1 Plasmonic Nanoparticles
10.2.2 Brain Theranostics with Plasmonic Nanoparticles
10.2.3 Magnetic Nanoparticles
10.2.4 Brain Theranostics with Magnetic Nanoparticles
10.2.5 Advances in Brain Theranostics Using Magnetoliposomes
10.3 Conclusion and Future Perspectives
Part III: Development and Translation
11. Quality by Design for Nanocarriers
11.1 Introduction
11.2 The QbD Approach
11.2.1 QTPP
11.2.2 CQAs
11.2.3 Risk Assessment
11.3 Design of Experiments, Design Space and Control Strategy
11.3.1 Continuous Monitoring and Improvement
11.4 Conclusion
12. Recent in vitro Models for the Blood-Brain Barrier
12.1 Introduction to Blood-Brain Barrier Models
12.2 Microfluidic BBB Models
12.3 Cell Cultures
12.4 Model Assessment
12.4.1 Shear Stress
12.4.2 Barrier Permeability
12.4.3 Transepithelial Electrical Resistance
12.5 Concluding Remarks
13. Current in vivo Models for Brain Disorders
13.1 Introduction to Animal Models
13.2 Neurological Disease Animal Models
13.2.1 Neurodegenerative Diseases
13.2.2 Brain Tumours
13.2.3 Ischaemic Stroke
13.3 Animal Trials in the Development of Nanoparticles for CNS Disorders
13.4 Imaging Techniques for Nanoparticles: Diagnosis and Treatment
14. Modelling and Simulation of Nanosystems for Delivering Drugs to the Brain
14.1 Impact of Computational Approaches in the Design and Optimisation of Nanocarriers
14.2 Understanding BBB Permeability
14.3 Predicting Treatment Efficacy
14.4 Optimising Drug Delivery to the Brain
14.5 Concluding Remarks
15. Translational Challenges
15.1 Introduction
15.2 Translational Medicine
15.3 Nanoparticles as Carriers of Drugs
15.4 Nanotechnology: From the Diagnosis to the Treatment of Neurological Disorders
15.5 Clinical Applications of Nanoparticles in the Management of Brain Tumours
15.6 Challenges of Clinical Applications of Nanoparticles
15.7 The Importance of the Regulatory Pathway
Index