Table of Contents
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 Targeting Enzymes to Prevent Proliferation of Cancer Cells- Polo-Like Kinase 4 Inhibitor CFI-400945 Fumarate
6.5 Targeted Drug Delivery to Cancer
6.5.1 Affibody Molecules for Targeted Anticancer Therapy
6.5.2 Antibodies for Targeting of Radionuclides in Anticancer Therapy
6.5.3 Targaceutical Technology
6.5.4 PEGylated Liposomes
6.5.5 Genetic Targeting of Kinase Activity in Cancer Cells
6.5.6 Heat-Activated Targeted Drug Delivery
6.5.7 Novel Transporters to Target Photosensitizers to Cancer Cell Nuclei
6.5.8 Photodynamic Therapy of Cancer
6.5.9 Aptocine: A Photodynamic Cancer Vaccine?
6.5.10 Radionuclides Delivered with Receptor Targeting Technology
6.5.11 Transferrin for Drug Targeting to Cancer Cells
6.5.12 Lectins for Drug Targeting to Cancer Cells
6.5.13 Epidermal Growth Factor
6.5.14 Aptamer Mediated Drug Targeting
6.5.15 Tumour Targeting with Peptides
6.5.16 Antibody Based Targeting
6.5.17 Targeting Abnormal DNA in Cancer Cells
6.5.18 Targeted Delivery by Tumour-Activated Prodrug Therapy
6.5.19 Targeting Glutathione S-Transferase
6.5.20 Targeting Tumours by Exploiting Leaky Blood Vessels
6.5.21 Targeted Delivery of Anticancer agents with ReCODE™ Technology
6.5.22 Transmembrane Carrier Systems
6.5.23 Ultrasound and Microbubbles for Targeted Anticancer Drug Delivery
6.5.24 Ultrasound for Targeted Delivery of Chemotherapeutics
6.5.25 Vitamin Based Targeting for Cancer Chemotherapy
6.6 Strategies for Increasing Drug Penetration into Solid Cancers
6.6.1 Improving Drug Transport to Tumors
6.6.1.1 Combination Carbohydrate-Assisted Chemotherapy
6.6.1.2 Dextran Conjugates as Anticancer Drug Carriers
6.6.1.3 In situ Production of Anticancer Agents in Tumors
6.6.1.4 Electrochemotherapy
6.7 Cell-Based Drug Delivery in Cancer
6.7.1 Transduced Cells as Vehicles for Gene Delivery
6.7.2 Macrophages as Vehicles For Drug Delivery
6.7.3 Red Blood Cells as Vehicles For Drug Delivery
6.8 Chronotherapeutic Drug Delivery Systems (ChrDDs)
6.9 Angiogenesis and Drug Delivery to Tumors
6.9.1 Targeting Tumour Endothelial Cells
6.9.2 Vascular Targeting Agents as Cancer Therapeutics
6.9.3 Vascular Targeted Endoradiotherapy of Tumours using Alpha-Particle-Emitting Compounds
6.9.4 Targeted Delivery of Tissue Factor
6.10 Delivery of Proteins and Peptides for Cancer Therapy
6.10.1 CELLECTRA™ for Delivery of Cancer Vaccines
6.10.2 Emisphere’s Eligen™ System
6.10.3 Diatos DTS-201
6.10.4 Cationic Antimicrobial Peptides
6.10.5 Modification of Proteins and Peptides with Polymers
6.10.6 Peptidomimetics in Cancer Targeting
6.10.7 Peptide-Cytokine Complexes as Vascular Targeting Agents
6.10.8 Protein Transduction Technology
6.10.9 Cell Penetrating Peptides (CPPs)
6.11 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 Intracranial Drug Delivery
8.5.3 Intracerebroventricular Injection
8.5.4 Intrathecal Administration
8.5.5 Implants for Drug Delivery
8.5.6 Devices for Drug Delivery to the CNS
8.5.7 Convection-Enhanced Delivery (CED) to the CNS
8.5.8 Drug Delivery from Biological Tissues
8.5.9 Intra-Arterial Drug Delivery to the Brain
8.5.10 Direct Injection into the CNS Substance or CNS Lesions
8.5.11 Intraventricular Injection of Drugs
8.5.12 Bacteriophage as CNS Therapeutics
8.5.13 Intrabodies
8.6 Delivering Gene Therapy to the Brain
8.6.1 Introduction
8.6.1.1 Glioblastoma- A Case Study Using Viral Vectors
8.6.1.2 Cytotoxic Gene Therapy
8.6.1.3 Stem cells as Oncolytic Virus Carriers
8.6.1.4 Suicide Gene Prodrugs
8.6.1.5 Immune Stimulation
8.6.1.6 Anti-Angiogenesis Strategies
8.6.1.7 Non- Viral Vectors for Gene Therapy Delivery to the Brain
8.2.1.8 Trojan Horse Liposomes
8.6.2 Targeting Antisense to the Brain
8.6.2.1 Antisense Therapy
8.6.2.2 Trojan Horse Liposomes- Targeting Antisense RNA Gene in Brain Cancer
8.6.2.3 High-Flow Microinfusion into the Brain Parenchyma
8.6.2.4 Introduction of Antisense Compounds into the CSF Pathways
8.6.2.5 Biodistribution of Antisense Compounds Following Intrathecal Administration
8.6.2.6 Intracerebroventricular Administration of Antisense Oligonucleotides
8.6.3 Targeting RNA Interference (RNAi) to the Brain
8.6.3.1 THL Targeting of an RNAi Gene in Brain Cancer
9.0 Drug Delivery for Treatment of Neurological Disorders
9.1 Parkinson’s disease
9.1.1 Targeted Therapies for Parkinson’s Disease
9.1.1.1 Intracerebral Administration of GDNF
9.1.1.2 Liposomes in Parkinson’s Disease
9.1.1.3 Bolaamphiphiles and V-Smart Technology
9.1.1.4 Trojan Horse Liposomes: Targeting a Therapeutic Gene in Parkinson’s Disease
9.1.1.5 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 Galectin Therapeutics
15.31 Genentech Inc.
15.32 Genmab AS
15.33 Genzyme
15.34 Gilead
15.35 GlaxoSmithKline
15.36 Icon Bioscience
15.37 ImmunoGen Inc.
15.38 Inovio Pharmaceuticals Inc.
15.39 Insmed
15.40 Janssen Pharmaceuticals
15.41 King Pharma
15.42 Ligand/Chiva
15.43 Light Sciences Oncology
15.44 Eli Lilly and Co.
15.45 Merck
15.46 Nanocarrier
15.47 Neopharma
15.48 Northern lipids
15:49 Novartis
15.50 Pfizer
15.51 PharmAthene
15.52 Phosphorex
15.53 pSivida corp
15.54 Purdue
15.55 Roche
15.56 RP Scherer Int /BTG
15.57 Salix Pharma
15.58 Samyang biopharm
15.59 sigma-tau
15.60 Skyepharm ENDO
15.61 Spectrum Pharmaceuticals Inc.
15.62 Spectrum/Talon
15.63 Spherotech
15.64 Surmodics
15.65 Takeda
15.66 Terumo
15.67 TTY Biopharma
15.68 United Therapeutics
15.69 Zeneus (TEVA)
15.70 Zimmer Biomet
16.0 Current Targeted Drug Delivery Products on the Market
17.0 In-Depth SWOT Analysis of the Targeted Drug Delivery Market
17.1 Drivers of the Market
17.1.1 Will Patent Expirations and Introduction of New Technologies Drive the Short Term Market?
17.1.2 Increased Patient Compliance Rates
17.1.3 Increased Incidence of Chronic Conditions and Prevalence Rates
17.1.4 Increased Drug Administration Requirements
17.2 Restraints and Weaknesses of the Advanced and Targeted Drug Delivery Market
17.2.1 Technical Restraints
17.2.2 Drug Adverse Reactions
17.2.3 Drug Failures
17.3 Opportunities Within the Market Place
17.3.1 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
