Advanced & Targeted Drug Delivery Global Market to 2020
Bioactivation, Monoclonal Antibodies, liposomes, microspheres, nanoparticles, nanotherapeutics,
nanocarrier systems, water-soluble particles and macromolecular drugs, ADEPT (Antibody Directed
Enzyme Prodrug Therapy), VDEPT (Virus Directed Prodrug Enzyme Therapy) and chemical drug
delivery systems
1.0
Executive Summary
1.1
Objectives of Report
1.2
Data Sources & Methodology
1.3
Key Findings & Observations
2.0
Drug Delivery
2.1
Introduction
2.1.1 Pharmacokinetics
2.1.2 Bioavailability
2.2
Process of Drug Absorption
2.2.1 Epithelial Cells
2.2.2 Epithelial Cell Junctions
2.2.3 Drug Absorption Routes
2.2.3.1 Passive Diffusion
2.2.3.2 Facilitated Passive Diffusion
2.2.3.3 Active Transport
2.2.3.4 Endocytic Engulfment
2.2.3.5 Efflux Systems
2.3
Physicochemical Properties of Drugs that Influence Absorption
2.3.1 Partition Coefficient
2.3.2 Prodrugs
2.3.3 Drug Ionization
2.3.4 Molecular Weight
2.3.5 Solubility
2.3.6 Stability
2.4
Pharmacokinetic Process
2.4.1 Absorption
2.4.2 Distribution
2.4.3 Metabolism
2.4.3.1 Cytochrome p-450
2.4.3.2 Conjugation
2.4.4 Excretion
2.5
Controlled Release Drug Delivery
2.5.1 Zero-Order Controlled Release
2.5.2 Variable Release
2.6
Pharmacodynamics
2.6.1 Drug-Receptor Interactions
2.6.2 Chemical Interactions
2.6.3 Dose-Response Relationships
2.7
Biotherapeutics
2.7.1 Proteins & Peptides
2.7.2 Nucleic Acids
2.7.2.1 Gene Therapy
2.7.2.2 Antisense Therapy
2.8
Conclusions
3.0
Advanced & Targeted Drug Delivery
3.1
Introduction
3.2
Rate Controlled Drug Release
3.2.1 Diffusion Controlled Release
3.2.1.1 Membrane-Controlled Devices
3.2.1.2 Polymer Matrix diffusion Controlled/ Monolithic Devices
3.2.2 Dissolution Controlled Release
3.2.2.1 Dissolution Controlled Reservoir
3.2.2.2 Dissolution Controlled Matrix
3.2.3 Osmosis Controlled Drug Release
3.2.4 Mechanical Controlled Drug Release
3.2.5 Bioresponsive Controlled Drug Release
4.0
Site Directed Drug-Targeting
4.1
Introduction
4.2
Essential Factors for Effective Drug Targeting
4.2.1 The Drug to be Delivered
4.2.2 The Drug Target
4.2.3 The Drug Delivery System
4.3
Physiological Barriers to Drug Targeting
4.3.1 Elimination of the Drug Carrier
4.3.1.1 Mononuclear Phagocyte System (MPS)
4.3.1.2 Opsonisation
4.3.2 Escape From the Circulation
4.4
Types of Drug Targeting
4.4.1 Passive Drug Targeting
4.4.1.1 Passive targeting by the MPS
4.4.1.2 Local Physiological Conditions
4.4.1.3 Enhanced Permeability and Retention (EPR) Effect
4.4.2 Active Drug Targeting
4.4.2.1 Folate Receptors
4.4.2.2 Transferrin Receptors
4.4.2.3 Antibodies
4.4.2.4 Lectin
4.4.2.5 Physical Targeting
4.5
Subcellular Drug Targeting
4.5.1 Targeting the Plasma Membrane
4.5.2 Membrane Trafficking
4.5.3 Targeting to Intracellular Compartments
4.5.3.1 Early Endosomes
4.5.3.2 Late Endosomes and Lysosomes
4.5.3.3 Endoplasmic Reticulum and Golgi Complex
4.5.4 Targeting the Cytosol
4.5.5 Targeting the Nucleus
4.5.6 Targeting Mitochondria
5.0
Carriers For Drug Targeting
5.1
Options for Drug Targeting
5.2
Modification of the Drug
5.2.1 Site Specific Localization
5.2.2 Site Specific Activation of Prodrugs
5.2.3 Antibody Directed Prodrug Therapy (ADEPT)
5.2.3.1 Gene Directed Prodrug Therapy (GDEPT)
5.2.3.2 Virus Directed Prodrug Therapy (VDEPT)
5.2.3.3 Polymer-Directed Enzyme Prodrug Therapy (PDEPT)
5.2.3.4 Clostridia-Directed Enzyme Prodrug Therapy (CDEPT)
5.3
Soluble Drug Carriers
5.3.1 Antibodies
5.3.1.1 Polyclonal Antibodies
5.3.1.2 Monoclonal Antibodies
5.3.1.3 Immunoconjugates
5.3.1.4 Immunotoxins
5.3.1.5 Bispecific Antibodies
5.3.2 Polymeric Conjugates
5.3.2.1 Polymer Backbone
5.3.2.2 Linker
5.3.2.3 Drug
5.3.2.4 Targeting Polymer-Drug Conjugates
5.3.2.5 Small Cytotoxic Protein Neocarzinostatin (SMANCS)
5.3.3 Protein Drug Carriers
5.3.4 Polysaccharide Drug Carriers
5.4
Particulate Drug Carriers
5.4.1 Principles
5.4.2 Dendrimers
5.4.3 Solid Nanoparticles
5.4.3.1 Solid Lipid Nanoparticles
5.4.3.2 Solid Polymeric Nanoparticles
5.4.3.3 Solid Protein Nanoparticles
5.3.3.4 Inorganic Nanoparticles
5.4.4: Polymeric Micelles
5.4.5 Micro and Nanoemulsions
5.4.6 Liposomes
5.4.6.1 Conventional Liposomes
5.4.6.2 Long-Circulating Liposomes
5.4.6.3 Immunoliposomes
5.4.6.4 Cationic Liposomes
5.4.7 Microspheres
5.4.8 Poly(alkyl cyanoacrylate) Nanoparticles
5.4.9 Lipoprotein Carriers
5.4.10 Niosomes
5.4.11 TransfersomesTM
6.0
Targeted Drug Delivery in the Treatment of Cancer
6.1
Cancer Facts
6.2
Drug Targeting for Cancer
6.3
Local Drug Delivery Strategies for Cancer Treatment
6.3.1 Injection into the tumour
6.3.2 Antineoplastic Drug Implants into Tumours
6.3.3 OncoGel~PGLA/PEG Copolymer-Based Paclitaxel
6.3.4 Tumour Necrosis Factor Therapy
6.3.5 Direct Introduction of Anti-Cancer Agent into an Organ
6.3.6 Electrochemotherapy
6.3.6.1 Bleomycin
6.3.7 Enhancing Drug Delivery by Modulating Vascular and Interstitial Pressure
6.3.8 Convection Enhanced Drug Delivery and Brain Cancer
6.3.9 Paclimer Microspheres and Cancer
6.3.10 Expansile Nanoparticles
6.3.11 Chitosan Hydrogels
6.3.12 Polymer Millirods
6.3.13 Flexible Film Composites
6.3.14 Lipiodol-Drug Combination
6.3.15 DC Bead
6.3.16 Liposomal Gene therapy.
6.4
Selective Destruction of Cancer Cells
6.4.1 Sphingolipids
6.4.2 Hyperbaric Oxygen (HBO)
6.4.3 Selective Killing of Cancer Cells by Small Molecule Targeting the Stress Response
6.4.4
6.5
6.5.1
6.5.2
6.5.3
6.5.4
6.5.5
6.5.6
6.5.7
6.5.8
6.5.9
6.5.10
6.5.11
6.5.12
6.5.13
6.5.14
6.5.15
6.5.16
6.5.17
6.5.18
6.5.19
6.5.20
6.5.21
6.5.22
6.5.23
6.5.24
6.5.25
6.6
6.6.1
6.6.1.1
6.6.1.2
6.6.1.3
6.6.1.4
6.7
6.7.1
6.7.2
6.7.3
6.8
6.9
6.9.1
6.9.2
6.9.3
6.9.4
6.10
6.10.1
6.10.2
6.10.3
6.10.4
6.10.5
6.10.6
6.10.7
6.10.8
6.10.9
6.11
Targeting Enzymes to Prevent Proliferation of Cancer Cells- Polo-Like Kinase 4 Inhibitor
CFI-400945 Fumarate
Targeted Drug Delivery to Cancer
Affibody Molecules for Targeted Anticancer Therapy
Antibodies for Targeting of Radionuclides in Anticancer Therapy
Targaceutical Technology
PEGylated Liposomes
Genetic Targeting of Kinase Activity in Cancer Cells
Heat-Activated Targeted Drug Delivery
Novel Transporters to Target Photosensitizers to Cancer Cell Nuclei
Photodynamic Therapy of Cancer
Aptocine: A Photodynamic Cancer Vaccine?
Radionuclides Delivered with Receptor Targeting Technology
Transferrin for Drug Targeting to Cancer Cells
Lectins for Drug Targeting to Cancer Cells
Epidermal Growth Factor
Aptamer Mediated Drug Targeting
Tumour Targeting with Peptides
Antibody Based Targeting
Targeting Abnormal DNA in Cancer Cells
Targeted Delivery by Tumour-Activated Prodrug Therapy
Targeting Glutathione S-Transferase
Targeting Tumours by Exploiting Leaky Blood Vessels
Targeted Delivery of Anticancer agents with ReCODE™ Technology
Transmembrane Carrier Systems
Ultrasound and Microbubbles for Targeted Anticancer Drug Delivery
Ultrasound for Targeted Delivery of Chemotherapeutics
Vitamin Based Targeting for Cancer Chemotherapy
Strategies for Increasing Drug Penetration into Solid Cancers
Improving Drug Transport to Tumors
Combination Carbohydrate-Assisted Chemotherapy
Dextran Conjugates as Anticancer Drug Carriers
In situ Production of Anticancer Agents in Tumors
Electrochemotherapy
Cell-Based Drug Delivery in Cancer
Transduced Cells as Vehicles for Gene Delivery
Macrophages as Vehicles For Drug Delivery
Red Blood Cells as Vehicles For Drug Delivery
Chronotherapeutic Drug Delivery Systems (ChrDDs)
Angiogenesis and Drug Delivery to Tumors
Targeting Tumour Endothelial Cells
Vascular Targeting Agents as Cancer Therapeutics
Vascular Targeted Endoradiotherapy of Tumours using Alpha-Particle-Emitting Compounds
Targeted Delivery of Tissue Factor
Delivery of Proteins and Peptides for Cancer Therapy
CELLECTRA™ for Delivery of Cancer Vaccines
Emisphere's Eligen™ System
Diatos DTS-201
Cationic Antimicrobial Peptides
Modification of Proteins and Peptides with Polymers
Peptidomimetics in Cancer Targeting
Peptide-Cytokine Complexes as Vascular Targeting Agents
Protein Transduction Technology
Cell Penetrating Peptides (CPPs)
Targeted Delivery of Nucleic Acids for Cancer Therapy
6.11.1 Viral Vectors for Targeted Nucleic Acid Delivery
6.11.2 Non-Viral Vectors for Targeted nucleic acid Delivery
6.11.2.1
Monoclonal Antibodies
6.11.2.2
Transferrin
6.11.2.3
RGD Peptide
6.11.2.5
Aptamers
6.11.2.4
Folate Receptors
6.11.2.5.1
Aptamer-siRNA Chimeras in Prostate Cancer
6.11.2.6
Polysaccharides
6.11.3 Cell Mediated Targeting
6.11.3.1
Physical Targeting
6.11.3.1.1
Electroporation
6.11.3.1.2
Heat and Irradiation
6.11.3.1.3
Ultrasound
6.11.3.1.4
Magnetic Cell Mediated
6.11.3.1.5
Photochemical Internalization (PCI)
7.0
Targeted Drug Delivery for the Treatment of Infectious Disease
7.1
Tuberculosis
7.1.2 Global Impact of TB
7.1.3 Treatment of TB
7.1.4 TB and HIV
7.1.5 Multidrug-Resistant TB
7.1.6 Targeted Drug Delivery Methods for TB Therapy
7.1.6.1 Inhalable Antitubercular Drugs
7.1.6.2 Inhalable Dry Powder Formulations for TB Treatment
7.1.6.2.1
Liposomal Dry Powder
7.1.6.2.2
Microparticles
7.1.6.2.3
Nanoparticles
7.2
Malaria
7.2.1 Diagnosis and Treatment
7.2.2 Antimalarial Drug Resistance
7.2.3 Pathogenesis of Malarial Infection
7.2.4 Nanotechnology for the Treatment of Malaria
7.2.5 Lipid Based Nanocarriers for Antimalarials and Vaccines
7.2.5.1 Liposomes as Antimalarial Carriers
7.2.5.1.1
Conventional and Long-Circulating Liposomes
7.2.5.1.2
Negatively Charged Liposomes
7.2.5.2
Targeted Liposomes
7.2.5.3
Peptide Targeted Liposomes
7.2.5.4
Antibodies to Target Liposomes
7.2.5.5
Liposomes as Anti-Malarial Vaccine Adjuvants
7.2.5.6
SLNs as Carriers for Anti-Malarials
7.2.5.7
Emulsions as Carriers for Anti-Malarials
7.2.6 Polymers as Nanocarriers for Anti-Malarials
7.2.7 Other Nanocarriers for Anti-Malarials
7.2.7.1
Cyclodextrins and Inclusion Complexes with Anti-Malarials
7.2.7.2
Nanosuspensions as Carriers for Anti-Malarials
7.2.8 Nanocapsules
7.2.9 Drug Delivery to the Malaria Parasite Using an Arterolane-Like Scaffold (195)
7.2.10 Conclusions
7.3
HIV/AIDS
7.3.1 Treatment of HIV/AIDS
7.3.2 Targeting Strategies for the Delivery of Anti-HIV Drugs
7.3.2.1 Targeting the Virus
7.3.2.1.1
Glycoprotein-120
7.3.2.1.2
Glycoprotein-41
7.3.2.2 Targeting the Host Cell
7.3.2.2.1
Leukocyte Function Associated Antigen 1 (LFA-1)
7.3.2.2.2
Human Leukocyte Antigen (HLA)
7.3.2.2.3
C-type Lectin DC-SIGN
7.3.2.2.4
Cell Surface Glycoprotein CD4
7.3.2.2.5
Chemokine Receptor
7.3.2.2.6
Carbohydrate Binding Agents (CBAs)
7.3.2.2.7
Tuftsin
7.3.2.2.8
Transferrin
7.3.2.2.9
Aptamers
7.3.2.2.10
Low-density Lipoprotein (LDL)
7.3.2.3 Passive Targeting
7.3.2.4 Potential Targets
8.0
Targeted Drug Delivery by Physiological Region
8.1
Blood Brain Barrier
8.1.1
The Neurovascular Unit
8.1.2
Transport Across the Blood Brain Barrier
8.1.3
Biological and Pathological Properties of the Blood Brain Barrier for Drug Transport
8.2
Modern Methods for Drug Transport Across the Blood Brain Barrier
8.2.1 Opening Tight Junctions
8.2.2 Transport System Mediated Drug Delivery
8.2.2.1
Nanocarriers for Drug Delivery to the Brain
8.2.2.2
Aggregated Amphiphiles
8.2.2.3
IgG Fusion Proteins
8.2.3 Transport Vectors
8.2.4 Adsorptive Mediated Transcytosis
8.2.5 Receptor Mediated Transcytosis
8.2.6 Inhibition of Efflux Pumps by Pluronic® Block Copolymers
8.2.7 Cell Mediated Drug Transport
8.2.7.1
Microglial Cells
8.2.7.2
Neural Stem Cells
8.2.8 Cell Encapsulation Technology
8.3
Opening the Blood Brain Barrier For Drug Delivery
8.3.1 Osmotic Opening of the BBB
8.3.2 Focal Disruption of BBB by Ultrasound
8.3.3 Chemical Opening of the BBB
8.3.4 Rapid and Reversible Enhancement of BBB Permeability Using Lysophosphatidic Acid
8.3.5 Minimally Invasive Molecular Delivery Into the Brain Using Optical Modulation of Vascular
Permeability
8.3.6 Use of Nitric Oxide Donors to Open the BBB
8.3.7 Manipulation of the Sphingosine 1-Phosphate Receptor System
8.3.8 Application of Bradykinin-Analogue (RMP-7, Cereport® from Alkermes)
8.3.9 Transport Across the BBB by Short Chain Oligoglycerolipids
8.3.10 Peptide Masking
8.4.1 G-Technology®
8.4
Pharmacological Strategies to Enhance CNS Drug Delivery
8.4.2 Glycosylation Independent Lysosomal Targeting (GILT)
8.4.3 Chemical Structure Modification and Co-Administration of P-Glycoprotein Inhibitors
8.4.4 LipoBridge Technology
8.4.5 Exosome-Mediated Delivery of siRNA Into the Brain
8.4.6 2 B-Trans™ Technology in Gene Therapy of Alzheimer's Disease
8.4.7 Roche Brain Shuttle
8.5
Physical Strategies to Enhance CNS Delivery
8.5.1 Intranasal Delivery
8.5.2
8.5.3
8.5.4
8.5.5
8.5.6
8.5.7
8.5.8
8.5.9
8.5.10
8.5.11
8.5.12
8.5.13
8.6
8.6.1
8.6.1.1
8.6.1.2
8.6.1.3
8.6.1.4
8.6.1.5
8.6.1.6
8.6.1.7
8.2.1.8
8.6.2
8.6.2.1
8.6.2.2
8.6.2.3
8.6.2.4
8.6.2.5
8.6.2.6
8.6.3
8.6.3.1
9.0
9.1
9.1.1
9.1.1.1
9.1.1.2
9.1.1.3
9.1.1.4
9.1.1.5
Intracranial Drug Delivery
Intracerebroventricular Injection
Intrathecal Administration
Implants for Drug Delivery
Devices for Drug Delivery to the CNS
Convection-Enhanced Delivery (CED) to the CNS
Drug Delivery from Biological Tissues
Intra-Arterial Drug Delivery to the Brain
Direct Injection into the CNS Substance or CNS Lesions
Intraventricular Injection of Drugs
Bacteriophage as CNS Therapeutics
Intrabodies
Delivering Gene Therapy to the Brain
Introduction
Glioblastoma- A Case Study Using Viral Vectors
Cytotoxic Gene Therapy
Stem cells as Oncolytic Virus Carriers
Suicide Gene Prodrugs
Immune Stimulation
Anti-Angiogenesis Strategies
Non- Viral Vectors for Gene Therapy Delivery to the Brain
Trojan Horse Liposomes
Targeting Antisense to the Brain
Antisense Therapy
Trojan Horse Liposomes- Targeting Antisense RNA Gene in Brain Cancer
High-Flow Microinfusion into the Brain Parenchyma
Introduction of Antisense Compounds into the CSF Pathways
Biodistribution of Antisense Compounds Following Intrathecal Administration
Intracerebroventricular Administration of Antisense Oligonucleotides
Targeting RNA Interference (RNAi) to the Brain
THL Targeting of an RNAi Gene in Brain Cancer
Drug Delivery for Treatment of Neurological Disorders
Parkinson's disease
Targeted Therapies for Parkinson’s Disease
Intracerebral Administration of GDNF
Liposomes in Parkinson’s Disease
Bolaamphiphiles and V-Smart Technology
Trojan Horse Liposomes: Targeting a Therapeutic Gene in Parkinson’s Disease
Delivery of Cerebral Dopamine Neurotrophic Factor with Microbubbles and
Ultrasound
9.1.1.6
Using Exosomes to Deliver siRNA for Synuclein Knockdown
9.1.1.7
Targeted Drug Delivery for Parkinsons’s Disease
9.1.1.8
Cell Therapy for Parkinson’s Disease
9.1.1.8.1
Porcine Xenograft
9.1.1.8.2
Encapsulated Cells
9.1.1.8.3
Stem Cells
9.1.1.8.4
Human Retinal Pigment Epithelium Cells
9.1.1.9
Gene Therapy for Parkinson Disease
9.1.1.10
Convection Enhanced Drug (CED) Delivery in Parkinson’s Disease
9.2
Alzheimer’s Disease
9.2.1 Drug Delivery for Alzheimer’s Disease
9.2.1.1
Perispinal Etanercept (172)
9.2.1.2
Debio 9902 (ZT-1) for Alzheimer´s Disease
9.2.1.3
Brain Derived Neurotrophic Factor (BDNF) for Alzheimer’s Disease
9.2.1.4
Chemical Modification of Disease Therapeutic Peptides
9.2.1.5
Liposomes for Drug Delivery in Alzheimer’s Disease
9.2.1.6
Convection Enhanced Drug (CED) Delivery in Alzheimer’s Disease
9.2.2 Cell and Gene Therapy for Alzheimer Disease
9.2.2.1
Encapsulated Cell Therapy in Alzheimers Disease
9.2.2.2
RNAi therapy of Alzheimer's Disease
9.3
Huntington's Disease
9.3.1 Treatment of Huntington's Disease
9.3.2 Gene therapy of Huntington's Disease
9.3.2.1
Using Encapsulated Cells to Treat Huntington's Disease
9.3.2.2
Adeno-Associated Viral Vector Mediated Administration of Neurotrophic Factors
9.3.2.3
Nucleotide Therapeutics for Huntingtin’s Disease Treatment
9.4
Amyotrophic Lateral Sclerosis (ALS)
9.4.1 Treatment of ALS
9.4.2 Gene and Antisense Therapy of ALS
9.4.3.1
Familial ALS
9.4.3.2
Sporadic ALS
9.5
Stroke
9.5.1 Targeted Drug Delivery to Obstructed Blood Vessels Using Nanotherapeutics
9.5.2 Drug Delivery for Prevention of Restenosis of Carotid Arteries
9.5.2.1
Targeted Local Anti-Restenotic Drug Delivery
9.5.2.2
Intraluminal Drug Delivery
9.5.2.2.1
Drug-Eluting Stents (DES)
9.5.2.2.2
Drug-Eluting Balloons (DEBs)
9.5.2.2.3
Porous and Microporous Balloon
9.5.2.3 Gene Therapy to Prevent Restenosis
9.5.2.4 Nanoparticle Drug-Eluting Stents
9.5.2.5 Nanoparticle Gene-Eluting Stents
9.5.3 Stem Cell Transplant to the Brain
9.6
Multiple Sclerosis
9.6.1 Delivery of Methylprednisolone Across the Blood Brain Barrier
9.6.2 Cell therapy for MS
9.6.3 Treatment of MS Through Selective Repression of the Immune System
9.6.4 Nucleic Acid Therapeutics for the Treatment of MS
9.6.4.1
Gene therapy for MS
9.6.4.2
Antisense for MS ~ATL1102
9.7
Epilepsy
9.7.1 Methods of Delivery of Novel Antiepileptic Therapies
9.7.1.1
Nanocarrier Based Drug Delivery for Epilepsy
9.7.1.2
Prodrugs for Epilepsy
9.7.1.3
Targeting Anti-Epilepsy Drugs
9.7.1.4
Nasal Administration of Anti-Epilepsy Drugs
9.7.1.5
Intracerebral administration of Anti-Epilepsy Drugs
9.7.2 Cell Therapy of Epilepsy
9.7.3 Gene Therapy for Epilepsy
9.8
Migraine
9.8.1 Monoclonal Antibodies for the Prevention of Migraine
10.0
Targeted Drug Delivery to the Lung
10.1
Why Target the Lung?
10.2
Targeting Specific Lung Regions
10.3
Particle Size and Deposition
10.3.1
Small Molecules
10.3.1.1
Hydrophobic Small Molecules
10.3.1.2
Hydrophilic Small Molecules
10.3.2 Macromolecules
10.4
Nanoparticles
10.4.1
Delivery of Nanoparticles using Dry Powder Carriers
10.4.2
Delivery of Nanoparticles using Nebulisation
10.5
Targeting by Cell Surface Interactions
10.6
Nanoparticle Based Gene Delivery to Lungs
11.0
Targeted Drug Delivery to the Skin
11.1
Targeting Vaccines to the Skin
11.2
The Skin as an Immune Organ
11.2.1
Langerhans Cells- Epidermal Antigen Presenting Cells
11.2.2
Keratinocytes- Immune Competent Epithelial cells
11.2.3
Dendritic Epidermal T Cells (DETC) γδ T cells -Specialised Resident Epithelial Cells
11.2.4
Epidermotropic T lymphocytes-Circulating T Cells that home to the Epidermis
11.2.5 Melanocytes-Epidermal Pigment Cells With Immune Properties
11.3
Vaccine Delivery to the Skin
11.3.1
Dissolvable Microneedle Array
11.3.2
Electroporation for Administering DNA Vaccines
11.3.3
Microneedles for Transdermal Vaccine Delivery
11.3.4
Needle-Free Delivery of Vaccines
11.4
Applications for Transdermal Vaccination
11.4.1
HIV/AIDS Vaccine
11.4.2
Transdermal DNA Influenza Vaccine
12.0
Targeted Drug Delivery to The Retina
12.1
Structure of the Retina
12.2
Drug Delivery to the Retina
12.2.1
Systemic
12.2.2
Topical
12.2.3
Intravitreal Injection
12.2.3.1
Liposomes
12.2.3.2
Microspheres/Nanospheres
12.2.3.3
Microemulsions and Dendrimers
12.2.3.4
Verisome
12.2.4
Intravitreal Implants
12.2.5
Scleral Drug Delivery
12.2.5.1
Scleral plugs and Implants
12.2.5.2
Subconjunctival Injections
12.2.6
Suprachoroidal Drug Delivery
12.2.6.1
Microcatheter
12.2.6.2
Hollow Microneedles
12.2.7
Encapsulated Cell Technology
12.2.7.1
NT-501
12.2.7.2
NT-503
12.2.8
Sustained Release Refillable Options
12.2.8.1
MicroPump
12.2.8.2
Port Delivery System
12.3
Transporter Mediated Drug Delivery to the Retina
12.3.1 Strategies to Improve Ocular Bioavailability by Transporter Mediated Drug Delivery
13.0
Targeting The Colon
13.1
Achieving Site-Specific Drug Delivery to the Colon
13.1.1 Primary Approaches
13.1.1.1
pH Sensitive Drugs
13.1.1.2
Time Controlled Release Systems (TCRS)
13.1.1.3
Microbially Triggered
13.1.1.4
Prodrug Approach
13.1.2 Novel Approaches
13.1.2.1
Pressure Controlled Drug Delivery
13.1.2.2
Osmotic Controlled Drug Delivery (OROS-CT)
13.1.2.3
Novel Colon Targeted Delivery System (CODES™)
14.0
Global Market for Targeted Drug Delivery
14.1
Global Drug Delivery Market
14.2. Overview and Analysis
14.3
Advanced Drug Delivery Market by Geography
14.4
USA Drug Delivery Market
14.5
European Drug Delivery Market
14.6
Emerging Drug Delivery Markets
14.7
The Advanced Drug Delivery Landscape
14.8
Advanced Drug Delivery Market by Therapeutic Area
14.9
Cancer
14.10 Infectious Disease
14.11 Blood Brain Barrier Neurological
14.12 Lung
14.13 Skin
14.14 Colon
14.15 Retina
14.16 Advanced Drug Delivery Market By Technology
15.0
Company Business Profiles, Strategic Evaluation & Financial Analysis
15.1
Abbott/Abbvie
15.2
Adare Pharma
15.3
Allergan
15.4
Alza
15.5
American Biosciences
15.6
Amgen
15.7
Astellas/Gilead
15.8
Astra Zeneca
15.9
Auritec pharma
15.10 Avanti Polar Lipids
15.11 Bausch and Lomb
15.12 Bayer
15.13 BBB Therapeutics
15.14 Becton, Dickinson and Company
15.14 Berna Biotech
15.15 Bicycle Therapeutics
15.16 BioDelivery Sciences International
15.16 Biogen
15.17 Boston Scientific
15.18 Bristol-Myers Squibb Company
15.19 BTG plc
15.20 Celsion Corp
15.x
Cytogel Pharma
15.21 D-Pharm Ltd
15.22 Debiopharm
15.x
Debiotech
15.23 Dendritech
15.24 Domantis/GSK
15.25 Eisai
15.x
Eksigent
15.26 Encapsula nanosciences
15.27 Endo International
15.28 Enzon
15.29 f-star
15.x
Flamel Technologies
15.30
15.31
15.32
15.33
15.34
15.35
15.36
15.37
15.38
15.39
15.40
15.41
15.42
15.43
15.44
15.45
15.46
15.47
15.48
15:49
15.50
15.51
15.52
15.53
15.54
15.55
15.56
15.57
15.58
15.59
15.60
15.61
15.62
15.63
15.64
15.65
15.66
15.67
15.68
15.69
15.70
16.0
17.0
17.1
17.1.1
17.1.2
17.1.3
17.1.4
17.2
17.2.1
17.2.2
17.2.3
17.3
17.3.1
Galectin Therapeutics
Genentech Inc.
Genmab AS
Genzyme
Gilead
GlaxoSmithKline
Icon Bioscience
ImmunoGen Inc.
Inovio Pharmaceuticals Inc.
Insmed
Janssen Pharmaceuticals
King Pharma
Ligand/Chiva
Light Sciences Oncology
Eli Lilly and Co.
Merck
Nanocarrier
Neopharma
Northern lipids
Novartis
Pfizer
PharmAthene
Phosphorex
pSivida corp
Purdue
Roche
RP Scherer Int /BTG
Salix Pharma
Samyang biopharm
sigma-tau
Skyepharm ENDO
Spectrum Pharmaceuticals Inc.
Spectrum/Talon
Spherotech
Surmodics
Takeda
Terumo
TTY Biopharma
United Therapeutics
Zeneus (TEVA)
Zimmer Biomet
Current Targeted Drug Delivery Products on the Market
In-Depth SWOT Analysis of the Targeted Drug Delivery Market
Drivers of the Market
Will Patent Expirations and Introduction of New Technologies Drive the Short Term Market?
Increased Patient Compliance Rates
Increased Incidence of Chronic Conditions and Prevalence Rates
Increased Drug Administration Requirements
Restraints and Weaknesses of the Advanced and Targeted Drug Delivery Market
Technical Restraints
Drug Adverse Reactions
Drug Failures
Opportunities Within the Market Place
High Number of Pharmaco & Drug Delivery Company Collaboration
17.4
Challenges and Barriers to Market Entry
18.0
Future Developments and Outlook
Appendix 1: Further Reading & Bibliography
List of Tables & Figures (as of Dec 3rd 2015)
Table 2.1: Causes of Low Bioavailability
Table 2.2: Sulfamethazine Formulation (IV, Oral Solution, Rapid Release Tablet and Sustained
Release Tablet) Area Under Curve Comparison
Table 2.3: Bioavailability Terminology
Table 2.4: Epithelial Cell Type Associated with Drug Delivery Sites
Table 2.5: Type, Functional and Biological Properties of Epithelial Cell-to-Cell Junctions
Table 2.6: Barbiturate Absorption in Rat Colon and Partition Coefficient
Table 2.7: Number of Hydrogen Bonds Formed by Functional Groups
Table 2.8: Classification, Bioactivation Site, Tissue Location and Examples of Prodrugs
Table 2.8: Strategies to Increase Drug Solubility
Table 2.9: Defining Basic Pharmacokinetic Properties by Formula and Parameter
Table 2.10: Factors Affecting Drug Distribution Rates
Table 2.11: Enzymes Involved in Drug Metabolism
Table 2.12: Substances that Interact with CYP1A2 Isofom of Cytochrome p450
Table 2.13: Variable Release Drug Delivery for Circadian Rhythms, Changing Metabolism and
Pulsatile Release
Table 2.14: Examples of Physiologic and Drug-Receptor Proteins
Table 2.15: Selected Biotherapeutics by Indication, Technology and Mechanism of Action
Table 2.16: Protein Stability Problems in Vitro
Table 2.17: Protein Stability Problems in Vivo
Table 2.18: Limitations Affecting Drug Efficacy
Table 3.1: Systemic and Intracellular Drug Targeting
Table 3.2: Polymer Membrane Permeation Controlled Drug Delivery Systems
Table 3.3: Biodegradable Controlled Release Systems
Table 3.4: Commercially Available Osmotic Drug Delivery Systems
Table 3.5: Osmotic Drug Delivery Systems on the Market
Table 3.6: Implantable Osmotic Devices
Table 4.1: Characteristics of Ideal Drug Targeting System
Table 4.2: Components of Parenteral Drug Delivery & Targeting System
Table 4.3: Biological Sites for Optimal Drug Targeting
Table 4.4: Biological Functions of the Mononuclear Phagocyte System (MPS)
Table 4.5: Factors Affecting Particle Clearance by the Mononuclear Phagocyte System (MPS)
Table 4.6: Therapeutics Exploiting the Enhanced Permeability and Retention (EPR) Effect
Table 4.7: Ligands and Their Respective Receptors on Various Cell Types
Table 4.8: Monoclonal Antibodies used for Cancer Treatment
Table 4.9: Drugs Directed to Subcellular Targets and their Applications
Table 4.10: Endocytic Mechanisms for Drug Delivery
Table 5.1: Drug Delivery Systems and Mechanisms for Drug Targeting
Table 5.2: Factors Affecting Choice of Drug Carrier
Table 5.3: Prodrugs for Targeted Drug Delivery
Table 5.4: Considerations for Antibody Directed Prodrug Therapy (ADEPT)
Table 5.5: Therapeutic Polyclonal Antibodies
Table 5.6: Licensed Monoclonal Antibodies by Target, Type, Approval Date and Indications
Table 5.7: Clinically Used Immunoconjugates by Source and Indication
Table 5.8: Types of Immunoconjugates by Mechanism and Indication
Table 5.9: Selected Companies Producing Bispecific Antibodies by Technology Platform and
Mechanism
Table 5.10: Advantages of Polymer-Drug Conjugates
Table 5.11: Examples of Drug-Polymer Conjugate Agents
Table 5.12: Synthetic, Natural and Pseudosynthetic Polymers for Drug Conjugation
Table 5.13: Mechanisms of Linker Cleavage
Table 5.14: Advantages and Disadvantages of Particulate Drug Carriers
Table 5.15: Pharmacokinetics of Dendrimers
Table 5.16: Therapeutic Applications for Dendrimers
Table 5.17: Therapeutic Applications For Inorganic Nanoparticles
Table 5.18: Drug Loading
Table 5.19: Characteristics of Polymeric Micelles
Table 5.20: Advantages and Drug Examples of Polymeric Micellar Systems
Table 5.21: Advantages and Disadvantages of Micro-Emulsions
Table 5.22: Comparison of Microemulsion with Conventional Emulsion Properties
Table 5.23 Pharmacokinetic Studies of Microemulsions for Brain Targeting
Table 5.24: Marketed Liposomal and Lipid-Based Products and those in Clinical
Development
Table 5.25: Types and Characteristics of Liposomes
Table 5.26: Ligand-Targeted vs. Passively Targeted Liposomes
Table 5.27: Synopsis of General Principles of Nucleic Acid Delivery Using Liposomes
Table 5.28: Lipoprotein Characteristics
Table 5.29: Lipoprotein Carrier Overview of Diagnostic and Therapeutic Applications
Table 5.30: Comparison of Liposomes and Niosomes
Table 6.1: Targeted and Non-Targeted Cancer Therapies
Table 6.2: Classification of Targeted Drug Delivery Processes
Table 6.3: Strategies for Targeted Drug Delivery in Cancer
Table 6.4: TNF-Based Locoregional Treatments for Locally Advanced Solid Tumours: Worldwide
Clinical Experience
Table 6.5: Flexible Film Composites
Table 6.6: Potential Sphingolipid-Related Targets for Improving Antitumour Therapeutic Efficacy
Table 6.7: Preclinical and Clinical Studies Related to Enhancing Therapeutic Efficacy via Modulation
of Sphingolipid Metabolism
Table 6.8: Hyperbaric Oxygen (HBO) Therapy Studies
Table 6.9: Studies Using HBO For the Treatment of Cancer
Table 6.10: Classification of Targeted Drug Delivery Processes
Table 6.11: Clinically Applied Photosensitisers
Table 6.12 Advantages & Disadvantages of Photodynamic Therapy
Table 6.13: Combinations of PDT and Various Therapeutic Modalities in Cancer Treatment: A
Comprehensive Summary
Table 6.14: Commercially Approved Radioimmunotherapy Agents
Table 6.15: Research Studies using Transferrin Conjugates for Targeted Drug Delivery
Table 6.16: Lectins in Targeted Drug Delivery
Table 6.17: Research Studies using Transferrin Conjugates for Targeted Drug Delivery
Table 6.18: Research Studies using Transferrin Conjugates for Targeted Drug Delivery
Table 6.19: Aptamers Isolated for Cancer Therapeutics.
Table 6.20: Research Studies using Peptide Conjugates for Targeted Drug Delivery
Table 6.21: FDA Approved monoclonal Antibodies to Target Cancer
Table 6.22: Research Studies using Antibody Conjugates for Targeted Drug Delivery
Table 6.23: Small Molecule Inhibitors of DNA Damage Response Factors in Preclinical or Clinical
Development for Cancer Therapy
Table 6.24: PARP Inhibitors in Preclinical or Clinical Development for Cancer Therapy
Table 6.25: Tumor Activated Prodrugs
Table 6.26: Examples of Tumor Accumulation of Macromolecules & Nanoparticles
Table 6.27: Summary of Ultrasound-Targeted Microbubble Destruction (UTMD) in Tumor Therapy
Table 6.28: Research Studies using Ultrasound for Targeted Drug Delivery
Table 6.29: Methods Used for Studying Drug Penetration
Table 6.30: Other Carbohydrate Derived Chemotherapeutics
Table 6.31: Advantages of Dextrans as Drug Carriers
Table 6.32: Clinical Trial Data of Patient Outcomes Using Electrochemotherapy
Table 6.34: Transduced Cells for the Delivery of Biologics
Table 6.35: Advantages of Red Blood Cells as Drug Delivery Vehicles
Table 6.36: Chronotherapeutic Drug Delivery Systems (ChrDDs) on the Market
Table 6.37: Results of Phase III Clinical Trials Reporting Effects from Circadian-Based Treatments
Table 6.38: Research Studies Targeting Angiogenesis
Table 6.39: Tumor Vessel Markers for Ligand-Directed Vascular Targeting Agents
Table 6.40: Peptide Mediated Targeting of Cytokines to Tumor Vasculature
Table 6.41: Targeting Sequences Coupled to Cell Penetrating Peptides for delivery to Tumours
Table 6.42: Activatable Cell Penetrating Peptides
Table 6.43: Transducible Agents of Cell Penetrating Peptides
Table 6.44: Comparison of Oligonucleotide Therapeutics
Table 6.45: Challenges for Nucleic Acid Delivery
Table 6.46: Monoclonal Antibody Mediated Targeting of Nucleic acids
Table 6.47: Transferrin Mediated Targeting of Nucleic acids
Table 6.48: RGD Peptide Mediated Targeting of Nucleic acids
Table 6.49: Folate or Aptamer Mediated Targeting of Nucleic Acids
Table 6.50: Sugar and Polysaccharide Mediated Targeting of Nucleic Acids
Table 7.1: Tuberculosis Facts
Table 7.2: Drugs used for TB Therapy
Table 7.3: Liposomal Dry Powders for Drug Delivery in TB
Table 7.4: Microparticles for Delivery of Anti-TB Drugs
Table 7.5: Nanoparticles for Delivery of Anti-TB Drugs
Table 7.6: Malaria Facts
Table 7.7: Conventional Antimalarial Drugs and Cellular Targets
Table 7.8: Formulation of Negatively Charged Liposomes
Table 7.9: HIV/AIDS Facts
Table 7.10: Limitations of Conventional Anti-Retroviral Therapy
Table 7.11: Targeting Glycoprotein gp120
Table 7.12: Targeting Glycoprotein gp41
Table 7.13: Targeting Leukocyte Function Associated Antigen 1 (LFA-1)
Table 7.14: Targeting Human Leukocyte Antigen
Table 7.15: Targeting CD4
Table 7.16: Targeting Chemokine Receptors
Table 7.17: Targeting Carbohydrate Binding Agents
Table 7.18: Targeting Tuftsin
Table 7.19: Targeting Transferrin
Table 7.20: Targeting with Aptamers
Table 7.21: Targeting with Low Density Lipoprotein LDL
Table 7.22: Targeted Nanocarriers for HIV Therapy
Table 8.1: Reasons for Blood Brain Barrier Low/Selective Permeability
Table 8.2: Impact of Common Disease States on the Blood Brain Barrier, and Corresponding Drug
Transport Opportunities
Table 8.3: Effect of Selected Stimuli/Agents on the BBB and Drug Transport
Table 8.4: Selected Examples of Nanoparticle Systems used for CNS Drug Delivery
Table 8.5: Summary of Drug Carriers Across the Blood Brain Barrier
Table 8.6: IgG Fusion Proteins Engineered for Targeted Brain Delivery
Table 8.7: Receptors used for Receptor Mediated Transcytosis Drug Delivery
Table 8.8: Examples of Cell Encapsulation for CNS and CNS-Related Diseases
Table 8.9: Advantages and Disadvantages of Unencapsulated, Microencapsulated, and
Macroencapsulated Cell Implants
Table 8.10: Intranasal Delivery of Neurotherapeutics
Table 8.11: Circumvention of the Blood-Brain Barrier to Enhance Delivery of Drugs to the CNS
Table 8.12: Disorders Where Intrabodies have Been or Could be Investigated
Table 8.13: Intrabodies and Antibody Fragments Targeting Disease Proteins of CNS Disorders
Table 8.14: Targeted Cytotoxic Gene Therapy
Table 8.15: Non-Viral Vectors for Gene Therapy to the Brain
Table 8.16: Gene Therapy-Based Clinical Trials for High Grade Gliomas
Table 8.17: Antisense Delivery Routes to the Brain
Table 8.18: Recent Studies Targeting Antisense to the Brain
Table 8.19: Recent Studies Targeting siRNA to the Brain
Table 8.20: Advantages and Disadvantages of siRNA Delivery Methods
Table 9.1: Parkinson’s Disease Facts
Table 9.2: Nanocarriers Intranasally Delivered Neurotherapeutics for Parkinson’s Disease
Table 9.3: Studies using Targeted Drug Delivery Systems for Parkinson’s Disease
Table 9.4: Alzheimer’s Disease Facts
Table 9.5: FDA Approved Alzheimer’s Drugs
Table 9.6: Future Key Targets for Alzheimer’s Drugs
Table 9.7: Effective Nanopharmaceuticals for Use in Alzheimer’s Disease
Table 9.8: Peptides with a Therapeutic Effect or that Reached the Brain in Alzheimer’s Disease
Animal Models
Table 9.10: Amyotrophic Lateral Sclerosis Facts
Table 9.11: Stroke Facts
Table 9.12: Management of Stroke
Table 9.13: Top Drug-Eluting Stents by Sales
Table 9.14: Advantages & Disadvantages of Intraluminal Drug Delivery Devices
Table 9.15: Gene Therapy Targets in Restenosis
Table 9.16: Preclinical Studies of Nanoparticle Drug-Eluting Stents for Coronary Restenosis
Table 9.17: Experimental Studies of Nanoparticle Gene-Eluting Stents for Coronary Restenosis
Table 9.18: Multiple Sclerosis Facts
Table 9.19: Advantages and Disadvantages of Different Cell Types for Treatment of MS
Table 9.20: Epilepsy Facts
Table 9.21: Epilepsy-Related Drug-Molecule Carrier Systems and Delivery Strategies
Table 9.22: Viral Gene Therapy Targets for Epilepsy
Table 9.23: Migraine Facts
Table 9.24: Popular Migraine Treatments
Table 10.1: Types of Inhalers for Drug Delivery to the Lung
Table 10.2: Animal Studies using Nanoparticles for Drug Delivery to the Lungs
Table 10.3: Summary of Pulmonary Delivery of Nanoparticles using Dry Powder Carriers
Table 10.4: Summary of Pulmonary Delivery of Nanoparticle Suspensions using Nebulisation
Table 11.1: Vaccines and Model Antigens used in Microneedle-based Vaccine Delivery Trials
Table 12.1: Advantages & Disadvantages of Intravitreal Injections
Table 12.2: Currently Available or Upcoming Intravitreal Drug Delivery Devices
Table 12.3: Transporter Mediated Drug Delivery to the Retina
Table 13.1: Colon Targeting: Diseases, Drugs and Sites
Table 13.2: Prodrugs Evaluated for Colon Specific Drug Delivery
Table 13.3: Azo-Polymeric Prodrugs
Table 13.4: Polysaccharides Investigated for Colon Specific Drug Delivery
Table 15.x: Bayer Therapeutic Areas of Interest
Table 15.x: Bayer’s Product Portfolio by Therapeutic Area
Table 15.x: Bayer Women’s Healthcare Product Portfolio
Table 15.x: Bayer Important Drug Candidates Currently Submitted for Approval
Table 15.x: Bayer Important Agents in R&D Development Stages and Clinical Phases
Table 15.x: Biogen’s Oncology Pipeline
Table 15.x: Bristol-Myers Squibb’s Pipeline Cancer Immunotherapy Products
Table 15.x: Endo International Milestones
Table 15.x: Endo International Product Portfolio
Table 15.x: Endo International Competitive Strengths
Table 15.x: Endo International Business Segments
Table 15.x: Endo International Acquisitions
Table 15.x: Genentech’s Cancer Immunotherapy Pipeline Products
Table 15.x: Genmab’s Products in Development
Table 15.x: GlaxoSmithKline Overview
Table 15.x: GlaxoSmithKline Objectives and Strategic Business Plan
Table 15.x: GlaxoSmithKline Financial Review FY2013
Table 15.x: GlaxoSmithKline Pharmaceuticals Sales by Therapeutic Area FY2013
Table 15.x: GlaxoSmithKline Vaccine Sales by Therapeutic Area FY2013
Table 15.x: GlaxoSmithKline Pharmaceuticals & Vaccines Sales Facts by Region FY2013
Table 15.x: GlaxoSmithKline Consumer Healthcare Sales by Therapeutic Area FY2013
Table 15.x: GlaxoSmithKline Pharmaceutical & Vaccine Turnover by Geographic Area FY2013
Table 15.x GlaxoSmithKline Core R&D Expenditure FY2013
Table 15.x GlaxoSmithKline Late Stage Pipeline Products
Table 15.x: Inovio Pharmaceuticals Product Pipeline
Table 15.x : Janssen Pharmaceuticals Therapeutic Areas of Interest
Table 15.x: Johnson & Johnson Pharmaceutical Division Therapeutic Areas of Interest
Table 15.x: Johnson & Johnson Top Performing Pharmaceutical Therapeutics FY2013
Table 15.x: Johnson & Johnson Top Performing New Pharmaceutical Therapeutics FY2013
Table 15.x Merck’s Pipeline of Cancer Immunotherapy Products
Table 15.x: Novartis Top Global Cancer Therapeutics and Mechanism of Action
Table 15.x: Novartis Top Global Primary Care Therapeutics and Mechanism of Action
Table 15.x: Novartis Top Global Established Care Therapeutics and Mechanism of Action
Table 15.x: Novartis Top Global Specialty Care Therapeutics and Mechanism of Action
Table 15.x: Novartis Top Global Integrated Hospital Care Therapeutics and Mechanism of Action
Table 15.x: Novartis Top Transdermal Drug Delivery Products
Table 15.x: Roche Holding’s Cancer Immunotherapy Product Pipeline
Table 16.1: Targeted Drug Delivery Products on the Market
Figure 2.1: Drug Bioavailability - Plasma Concentration Time Curve
Figure 2.2: Effect of Drug Formulation (IV, Oral Solution, Oral Tablet, Oral Slow Tablet) on Plasma
Concentration Time Curve
Figure 2.3: Classification of Epithelial Cells
Figure 2.4: Basic Types of Cell-to-Cell Junctions Between Epithelial Cells
Figure 2.5: Passive Diffusion
Figure 2.6: Ficks Law of Diffusion
Figure 2.7: Facilitated Diffusion
Figure 2.8: Primary Active transport -The Sodium Potassium Pump
Figure 2.9: Secondary Active Transport – Uniport, Symport and Antiport
Figure 2.10: Transport Processes Across Epithelial Barriers
Figure 2.11: Pro-Drug Conversion to Pharmacologically Active Drug
Figure 2.12: Entry of Different Drug Types into Cells
Figure 2.13: Absorption, Distribution, Metabolism and Excretion
Figure 2.14 Cytochrome p450 Isoforms Involved in Phase I Metabolism
Figure 2.15 Electron Shuttling to CYP P450 from NAPDH
Figure 2.16: Zero-Order Controlled Release
Figure 2.17: First Order, Zero Order and Pulsatile Release Drug Profiles
Figure 2.18: Dose-Response Curve for Ethanol
Figure 2.19: Gene Therapy Using an Adenovirus Vector
Figure 2.20: Preventing Protein Translation Using Antisense Technology
Figure 3.1: Matrix Monilithic Drug Delivery System
Figure 3.2: Dexedrine Spansule (Dextroamphetamine) 15mg capsule
Figure 3.3: Osmotic Delivery Device Pump System
Figure 3.4: Concerta Push-Pull Osmotic Release Oral System
Figure 3.5: Osmotic “Tablet” Alzet Pull-Push System
Figure 4.1: Drug Carrier Targeting Device
Figure 4.2: Targeted Dendrimer-Drug Monjugate Mechanism of Action
Figure 4.3: Particulate Liposome Drug Carrier
Figure 4.4: Important Factors in Opsonisation and Clearance
Figure 4.5: Capillary Wall Structures
Figure 4.6: Differences in Drug Distribution between Cancerous and Normal Tissues
Figure 4.7: Enhanced Permeability of the Endothelial Barrier at Sites of Inflammation and Tumours
Figure 4.8: Folate Receptor for Drug Targeting to Malignant Cells
Figure 4.9: Using Antibodies to Target Drugs
Figure 4.10: IgG Antibody Drug Conjugate
Figure 4.11: Fab and scFv Antibody Fragments
Figure 4.12 Endocytic Mechanisms for Drug Delivery
Figure 4.13: AB5 Toxins, Gangliosides and Polyomavirus Trafficking in the Endocytic pathway
Figure 5.1: The Antibody Directed Prodrug Therapy (ADEPT) System
Figure 5.2: Antibody IgG Structure
Figure 5.3: Types of Therapeutic Monoclonal Antibodies – Mouse, Chimeric, Humanized and Human
Figure 5.4: Immunoconjugate Structure
Figure 5.5: Antibody Fragments Currently in Development
Figure 5.6: Dendrimer Interior and Exterior Structure
Figure 5.7: Drug Incorporation Models of Solid Lipid Nanoparticles
Figure 5.8: Abraxane Structure
Figure 5.9: Polymeric Micelle Structure
Figure 5.10: Micellisation Model for an Amphiphilic AB-Diblock Copolymer
Figure 5.11: Forms of Microemulsion
Figure 5.12: Liposome Structure
Figure 5.13: How Liposomes Encapsulate and Carry Drugs
Figure 5.14: Liposome Classification
Figure 5.15: Niosome Structure
Figure 6.1: Number of Lung, Breast and Colorectal Cancer Diagnoses Globally, 2012
Figure 6.2: Global Cancer Statistics – Key Facts
Figure 6.3: Trends in Cancer Incidence Rates Among Men in the US 1975-2011
Figure 6.4: Global Cancer Incidence, Men 2012 (per 100,000)
Figure 6.5: Global Cancer Mortality, Men 2012 (per 100,000)
Figure 6.6: Trends in Cancer Incidence Rates Among Women in the US 1975-2011
Figure 6.7: Cancer Deaths in Women, Globally According to Cancer Type
Figure 6.8: Global Cancer Incidence, Women 2012 (per 100,000)
Figure 6.9: Global Cancer Mortality, Women 2012 (per 100,000)
Figure 6.10 Estimated Cancer Deaths in the US in 2015
Figure 6.11 Cancer Incidence Rates by Race and Ethnicity in the US 2007-2011
Figure 6.12 Cancer Incidence in Children (0-14yrs) and Adolescents (15-19yrs) 2007-2011
Figure 6.13: Global Incidence and Mortality of All Cancer Types (excl non-melanoma skin-cancer)
per 100,000, Male and Female
Figure 6.14: Combined Global Prostate, Breast, Colorectal, Lung and Bladder Cancer Incidence and
Mortality by Male and Female
Figure 6.15: Localised Chemotherapy Schematic
Figure 6.16: Intracavitary Gliadel Wafer Placement
Figure 6.17: Percutaneous Hepatic Perfusion
Figure 6.18: Ceramide-Mediated Apoptotic (Cell Death) Pathways
Figure 6.19: Schematic Stucture of Affitoxin
Figure 6.20 Aptocine’s Likely Immune Mechanism
Figure 6.21: Bystander effect for a labelled antibody
Figure 6.22: Zevalin® for the Treatment of Malignant lymphoma.
Figure 6.23: Endocytosis of the Transferrin Receptor
Figure 6.24: Lectins for Drug Targeting to Cancer Cells
Figure 6.25: Aptamers for Targeted Drug Delivery
Figure 6.26: Summary of Aptamer-Mediated Drug and siRNA Delivery Systems
Figure 6.27: ReCODE Technology
Figure 6.28: MARQIBO: Sphingomyelin/Cholesterol-Based Liposome–Encapsulated Vincristine
Figure 6.29: Ultrasound-Sensitive Carriers
Figure 6.30: Potential Reasons Why Cells Distant from Blood Vessels Might be Resistant to
Treatment
Figure 6.31: Multicellular Models and Their Use to Study Drug Penetration
Figure 6.32: Circadian Rhythms in Humans
Figure 6.33: Abnormalities in Tumor Endothelial Cells
Figure 6.34: Highly Efficient Electroporation Delivery of SynCon® Vaccine Enables
Best-in-Class
Immune Responses
Figure 6.35: MolMed Cancer Treatment Pipeline Products
Figure 7.1: The Life Cycle of Malaria
Figure 7.2: Drug Targets and Life Cycle of the HIV Virus
Figure 7.3: Virus-Based and Host Cell-Based Targets for Specific Targeting of HIV Infected Cells
Figure 7.4 Passive Targeting with Nanoparticles.
Figure 8.1: The Blood Brain Barrier and Neurovascular unit
Figure 8.2: Transport Routes Across the Blood Brain Barrier
Figure 8.3: Aggregates of Amphiphilic Molecules
Figure 8.4: Transport Pathways Into the Brain Following Intranasal Delivery
Figure 8.5: Summary of Strategies that Enhance Drug Delivery to the Brain
Figure 8.6: Gene Therapy Strategies for Brain Tumours
Figure 8.7: Preventing Protein Translation Using Antisense Technology
Figure 9.1: Steps Involved in the Synthesis and Release of Gamma Aminobutyric Acid (GABA)
Figure 9.2: Current Status of Different Gene Therapy Approaches in Parkinson’s Disease
Figure 9.3: Types of Stroke
Figure 9.4: Drug Eluting Stents
Figure 10.1: Why Target the Lung?
Figure 10.2: Factors that Determine the Deposition of Inhaled Particles
Figure 10.3: Regions of Particle Deposition According to Size
Figure 12.1 Cross Section of the Retina
Figure 12.2: Intravitreal Implants
Figure 12.3: ForSight Vision4 Port Delivery System
Figure 13.1: The pH Environment of the Human Gastrointestinal Tract
Figure 13.2: Common Bacteria Found in Various Parts of the GI tract
Figure 13.3: CODES™ Technology
Figure 15.x: Bayer Company Structure – Health Care, Crop Science and Material Science
Figure 15.x: GSK Turnover by Business FY2013
Figure 15.x: GSK Turnover by Region FY2013
Figure 15.x GSK Turnover by Segment FY2013
Figure 15.x GlaxoSmithKline Pharmaceutical Research & Development Investment FY2013
Figure 15.x Johnson & Johnson Total Sales by Business Division: Pharmaceuticals, Medical Devices
& Diagnostics, Consumer Health FY2013
Figure 15.x Johnson & Johnson Distribution of Sales – Pharmaceuticals, Medical Devices &
Diagnostics, Consumer Health FY2013
Figure 15.x Johnson & Johnson Pharmaceutical Segment Sales FY2013
Figure 15.x: Johnson & Johnson Medical Device and Diagnostic Sales FY2013
Figure 15.x Johnson & Johnson Consumer Healthcare Sales FY2013