Nanomedicines for Brain Drug Delivery

Preface to the Series
Preface
Contents
Contributors
Chapter 1: Biodegradable Polymeric Nanoparticles for Brain-Targeted Drug Delivery
	1 Introduction
	2 Design Principles of Commonly Employed Polymeric Nanoparticles for Brain Delivery
	3 Polymer Classes
		3.1 Polyesters
		3.2 Poly(Alkyl Cyanoacrylate)s (PACAs)
		3.3 Polysaccharides
	4 Polymeric Nanoparticle Preparation Techniques
		4.1 Emulsion/Solvent Evaporation Technique
		4.2 Double Emulsion/Solvent Evaporation Technique
		4.3 Nanoprecipitation Technique
		4.4 Emulsion Polymerization
		4.5 Ionic Gelation
	5 Particle Sizes of  PNPs
	6 Modifications of PNPs Surfaces for Improved Delivery to the Brain
		6.1 Particle Surface Properties
		6.2 Attachment of Targeting Ligands
	7 Conclusions
	References
Chapter 2: Liposomes as Brain Targeted Delivery Systems
	1 Introduction
	2 Liposomes
	3 Surface-Modified Liposomes
		3.1 Cerebral Ischemia
		3.2 Brain Tumors
		3.3 Alzheimer´s Disease
		3.4 Parkinson´s Disease
	4 Cationic Liposomes
		4.1 Untargeted Cationic Liposomes
		4.2 CPP-Decorated Liposomes
	References
Chapter 3: Nanofibers and Nanostructured Scaffolds for Nervous System Lesions
	1 Introduction
	2 The Nervous System
		2.1 Spinal Cord Injury
			2.1.1 Myelin-Associated Axon-Growth Inhibitors
			2.1.2 Spinal Cord Scarring and Axon-Growth-Repulsive Molecules
			2.1.3 Lesion-Induced Inflammation After Spinal Cord Injury
		2.2 Peripheral Nerve Injury
			2.2.1 Neuronal Cell Body Response
			2.2.2 Schwann Cell and Macrophage Responses to Injury
	3 Electrospinning
	4 Development of Bioengineered Nanofiber-Based Repair Strategies for Use in Spinal Cord Injury
		4.1 Substrates for In Vitro Analysis
		4.2 Implantable Scaffolds
		4.3 Artificial Dura Mater
	5 Development of ECM-Related Molecules and Hydrogels with Controlled Nanostructures and Properties for Use in Spinal Cord Inju...
		5.1 Injectable Hydrogels for Drug Delivery
		5.2 Injectable Hydrogels for Cell Delivery
		5.3 Injectable Hydrogels for the Presentation of Cell Binding/Signaling Motifs
		5.4 Injectable Hydrogels that Provide Guidance
	6 Development of Bioengineered Nanofiber-Based Structures for Use in Peripheral Nerve Injury
		6.1 Current FDA/CE-Approved Conduits and Scaffolds that Are Commercially Available for Peripheral Nerve Injury: Relative Advan...
		6.2 Nanofiber-Based Conduits for Peripheral Nerve Repair
		6.3 Advances in Nano-Scaffold Designs Intended to Control/Improve Cell-Substrate Interactions for Peripheral Nerve Repair
	7 Concluding Comments
	References
Chapter 4: Self-Assembling Peptide Nanofibrous Scaffolds in Central Nervous System Lesions
	1 Introduction
		1.1 Self-Assembling Peptide Nanofibrous Scaffolds
		1.2 Functionalized Self-Assembling Peptide Nanofibrous Scaffolds
	2 Materials
	3 Brain Injury Models and SAP Delivery Methods
		3.1 Traumatic Brain Injury
			3.1.1 Surgery Procedure
			3.1.2 Refill of the Damaged  Area
		3.2 Intracerebral Hemorrhage
			3.2.1 Surgery Procedure
			3.2.2 Intracranial Injection
		3.3 Other Surgical Brain Injury and SAP Delivery Methods
			3.3.1 Patching Up the Wound
			3.3.2 Other Combined Delivery Methods
	4 Conclusion
	References
Chapter 5: The Use of Peptide and Protein Vectors to Cross the Blood-Brain Barrier for the Delivery of Therapeutic Concentrati...
	1 Introduction
	2 Challenges for Brain Delivery Across the BBB
	3 Endogenous Mechanisms of BBB Penetration
	4 Current Therapeutic Approaches for BBB Penetration
		4.1 Invasive Approaches
			4.1.1 Convection-Enhanced Delivery
			4.1.2 Intracerebroventricular (ICV) Infusion; Intracerebral (IC) Injection; and Intrathecal (IT) Injection
			4.1.3 Polymer or Microchip Systems That Directly Release Therapeutics After Implantation
			4.1.4 Disruption of the BBB
				Using Osmotic Disruption
				Using Ultrasound
				Using Bradykinin and Analogs
		4.2 Pharmacological Approaches
		4.3 Physiological Approaches
			4.3.1 Transporter-Mediated Transport
				Carrier-Mediated Transporter
				Large Amino Acid Transporter 1 (LAT-1)
				GluT-1 and CD98hc Transporters
				Glutathione Transporters
			4.3.2 Receptor-Mediated Transport
				Transferrin Receptors (TR)
				Insulin Receptor (IR)
				Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1)
					Polysorbate 80-Coated Nanoparticles
					Melanotransferrin
					Receptor-Associated Protein
					Lentiviral Vector
					Angiopep
					Vect-Horus Peptide
			4.3.3 The BBB Transmigrating Llama Single-Domain Antibodies
			4.3.4 Receptor-Targeted Nanoparticles
				Trojan Horses Liposomes
				Nanoparticles Coated with Transferrin or Transferrin Receptor Antibodies
				Nanoparticles Modified With Synthetic Opioid Glycopeptide g7
			4.3.5 Adsorptive-Mediated Transcytosis
				Dendrimers
				Protein Transduction Domains
				Biologically Active Core/Shell Nanoparticles Designed for Drug Delivery Across the BBB
				Myristoylated Polyarginine Peptide (MPAP)
				Exosomes
		4.4 Intranasal Administration for Brain Delivery
	5 Conclusions
	References
Chapter 6: Inorganic Nanoparticles and Their Strategies to Enhance Brain Drug Delivery
	1 Introduction
	2 Gold Nanoparticles
	3 Iron Oxide Nanoparticles
	4 Carbon Nanotubes
	5 Silver Nanoparticles
	6 Silica Nanoparticles
	7 Quantum Dots
	8 Other Nanoparticles
	9 Conclusions
	References
Chapter 7: Magnetic Nanoparticles as Delivery Systems to Penetrate the Blood-Brain Barrier
	1 Introduction
	2 Magnetic Materials
	3 Iron Oxide Nanoparticles
	4 SPIONs as Systems with the Capacity to Penetrate the Brain
	5 Neurodegenerative Diseases
		5.1 Alzheimer´s Disease
		5.2 Parkinson´s Disease
		5.3 Huntington´s Disease
	6 Use of Magnetic Nanoparticles to Treat Brain Cancer
		6.1 Ligand Targeting of Magnetic Particles to Brain Cells
		6.2 Magnetic Targeting of Magnetic Particles to Brain Cells
		6.3 Use of Magnetic Nanoparticles to Generate Heat in the Brain
			6.3.1 Magnetic Hyperthermia
			6.3.2 Use of Magnetic Nanoparticles to Open the  BBB
	7 Use of Magnetic Nanoparticles to Treat NeuroAIDS
	8 Conclusions and Outlook
	References
Chapter 8: Nose-to-Brain Drug Delivery Enabled by Nanocarriers
	1 Introduction
	2 Proposed Pathways and Mechanisms of Direct Nose-to-Brain Drug Delivery
	3 Nanocarrier Enhancement of Nose-to-Brain Drug Delivery
		3.1 Effect of Nanocarrier Size Brain Targeting
		3.2 Effect of Nanocarrier Surface Charge on Brain Targeting
		3.3 Effect of Nanocarrier Material Composition on Brain Targeting
	4 Intranasal Nanocarriers for Diseases of the Central Nervous System
		4.1 Neurodegenerative Disorders
		4.2 Psychiatric Disorders
		4.3 Epilepsy
	5 Targeting the Olfactory Region in Humans
	6 Approaches for Developing Nanocarriers for Direct Nose-to-Brain Delivery
		6.1 In Vitro/Ex Vivo Permeation Studies
		6.2 In Vivo Brain Accumulation Studies
		6.3 Targeting the Olfactory Region
	7 Conclusion
	References
Chapter 9: In Vitro Models of Central Nervous System Barriers for Blood-Brain Barrier Permeation Studies
	1 Introduction
	2 Fundamentals and Composition of  BBB
		2.1 Molecular Properties of  BBB
	3 In Vitro BBB Permeation Measurement Methods
		3.1 Static BBB Models
			3.1.1 Monolayer BBB Models
			3.1.2 Co-culture BBB Models
		3.2 Dynamic BBB Models
			3.2.1 Cone-Plate BBB Apparatus
			3.2.2 Dynamic In Vitro BBB Model
			3.2.3 Microfluidic-Based BBB Models
	4 BBB Permeation Prediction Methods (In Silico Methods)
	5 Rationale for BBB Model Selection
	6 Conclusion and Future Aspects
	References
Chapter 10: Safety and Nanotoxicity Aspects of Nanomedicines for Brain-Targeted Drug Delivery
	1 Introduction
	2 General Nanotoxicity Mechanisms
	3 Nanoneurotoxicity
		3.1 Inorganic Nanoparticles
			3.1.1 Iron Oxide Nanoparticles
			3.1.2 Gold Nanoparticles
			3.1.3 Silver Nanoparticles
			3.1.4 Zinc Oxide Nanoparticles
			3.1.5 Titanium Dioxide Nanoparticles
		3.2 Carbon-Based Nanosystems
	4 Conclusion and Future Perspectives
	References
Index