Reportlinker Adds Drug Delivery in Central Nervous System Diseases - Technologies, Markets and Companies

Jun 07, 2010, 13:04 ET from Reportlinker

NEW YORK, June 7 /PRNewswire/ -- announces that a new market research report is available in its catalogue:

Drug Delivery in Central Nervous System Diseases - technologies, markets and companies


The delivery of drugs to central nervous system (CNS) is a challenge in the treatment of neurological disorders. Drugs may be administered directly into the CNS or administered systematically (e.g., by intravenous injection) for targeted action in the CNS. The major challenge to CNS drug delivery is the blood-brain barrier (BBB), which limits the access of drugs to the brain substance.

Advances in understanding of the cell biology of the BBB have opened new avenues and possibilities for improved drug delivery to the CNS. Several carrier or transport systems, enzymes, and receptors that control the penetration of molecules have been identified in the BBB endothelium. Receptor-mediated transcytosis can transport peptides and proteins across the BBB. Methods are available to assess the BBB permeability of drugs at the discovery stage to avoid development of drugs that fail to reach their target site of action in the CNS.

Various strategies that have been used for manipulating the blood-brain barrier for drug delivery to the brain include osmotic and chemical opening of the blood-brain barrier as well as the use of transport/carrier systems. Other strategies for drug delivery to the brain involve bypassing the BBB. Various pharmacological agents have been used to open the BBB and direct invasive methods can introduce therapeutic agents into the brain substance. It is important to consider not only the net delivery of the agent to the CNS, but also the ability of the agent to access the relevant target site within the CNS. Various routes of administration as well as conjugations of drugs, e.g., with liposomes and nanoparticles, are considered. Some routes of direct administration to the brain are non-invasive such as transnasal route whereas others involve entry into the CNS by devices and needles such as in case of intrathecal and intracerebroventricular delivery. Systemic therapy by oral and parenteral routes is considered along with sustained and controlled release to optimize the CNS action of drugs. Among the three main approaches to drug delivery to the CNS - systemic administration, injection into CSF pathways, and direct injection into the brain - the greatest developments is anticipated to occur in the area of targeted delivery by systemic administration.

Many of the new developments in the treatment of neurological disorders will be biological therapies and these will require innovative methods for delivery. Cell, gene and antisense therapies are not only innovative treatments for CNS disorders but also involve sophisticated delivery methods. RNA interference (RNAi) as a form of antisense therapy is also described.

The role of drug delivery is depicted in the background of various therapies for neurological diseases including drugs in development and the role of special delivery preparations. Pain is included as it is considered to be a neurological disorder. Cell and gene therapies will play an important role in the treatment of neurological disorders in the future.

The method of delivery of a drug to the CNS has an impact on the drug's commercial potential. The market for CNS drug delivery technologies is directly linked to the CNS drug market. Values are calculated for the total CNS market and the share of drug delivery technologies. Starting with the market values for the year 2009, projections are made to the years 2014 and 2019. The markets values are tabulated according to therapeutic areas, technologies and geographical areas. Unmet needs for further development in CNS drug delivery technologies are identified according to the important methods of delivery of therapeutic substances to the CNS. Finally suggestions are made for strategies to expand CNS delivery markets. Besides development of new products, these include application of innovative methods of delivery to older drugs to improve their action and extend their patent life.

Profiles of 71 companies involved in drug delivery for CNS disorders are presented along with their technologies, products and 69 collaborations. These include pharmaceutical companies that develop CNS drugs and biotechnology companies that provide technologies for drug delivery. A number of cell and gene therapy companies with products in development for CNS disorders are included. References contains over 400 publications that are cited in the report. The report is supplemented with 50 tables and 9 figures.


0.Executive Summary15

1.Basics of Drug Delivery to the Central Nervous System17


Historical evolution of drug delivery for CNS disorders17

Neuroanatomical and neurophysiological basis of drug delivery18

The cerebrospinal fluid18

The extracellular space in the brain19


Neuropharmacology relevant to drug delivery21

Introduction to neuropharmacology21


Absorption and distribution of drugs21

Drug metabolism and elimination22



Sites of drug action in the CNS22

Receptors coupled to guanine nucleotide binding proteins23

Acetylcholine receptor channels23

Dopamine receptors23

GABA receptor channels24

Glutamate receptor channels24

Non-competitive NMDA antagonists24

Serotonin receptors25

G-protein coupled receptors25

In vivo study of drug action in the CNS in human patients25


Brain imaging26

Chronopharmacology as applied to the CNS26

2.Blood Brain Barrier29


Features of the blood-brain barrier relevant to CNS drug delivery29

The neurovascular unit29

Functions of the BBB30

BBB as an anatomical as well as physiological barrier30

BBB as a biochemical barrier31

Genomics and proteomics of BBB31

Other neural barriers32

Blood-cerebrospinal fluid barrier32

Blood nerve barrier32

Blood-retinal barrier32

Blood-labyrinth barrier32

Passage of substances across the blood-brain barrier33

Transporters localized in the BBB33

Glucose transporter34

Amino acid transporters35

Ionic transporter35

Efflux transport systems35

BBB-specific enzymes36

Receptor-mediated transcytosis37

Lysophosphatidic acid-mediated increade in BBB permeability37

Folate transport system38

Molecular biology of the BBB38

Transport of peptides and proteins across the BBB38

Passage of leptin across the BBB38

Passage of cytokines across the BBB39

Passage of hormones across the BBB39

Passage of enzymes across the BBB40

Drugs that cross the BBB by binding to plasma proteins40

Current concepts of the permeability of the BBB40

Factors that increase the permeability of the BBB41

BBB disruption as adverse effect of vaccines for CNS disorders41

CNS disorders that affect the permeability of BBB42

Neurodegenerative disorders43

Mitochondrial encephalopathies44

Multiple sclerosis44

Central nervous system injuries44


Cerebrovascular disease45


Autoimmune disorders46

BBB and primary brain tumors46

BBB and cerebral metastases46

Testing permeability of the BBB47

In vitro models of BBB47

In vivo study of BBB48

Brain imaging48

In silico prediction of BBB49

Relevance of the BBB penetration to pharmacological action50

BBB penetration and CNS drug screening50


Transthyretin monomer as a marker of blood-CSF barrier disruption51

Evaluation of BBB permeability by brain imaging51

Biomarkers of disruption of blood-brain barrier51

Future directions for research on the BBB52

Application of genomics and proteomics to the study of BBB53

Use of neural stem cells to construct the blood brain barrier53

Strategies to cross the BBB53

3.Methods of Drug Delivery to the CNS55


Routes of drug delivery to the brain56

Delivery of drugs to the brain via the nasal route56

Nasal delivery of insulin-like growth factor-I57

Nasal delivery of midazolam57

Nasal delivery of hypocretin58

Intranasal administration of IFN beta-1b58

Nasal delivery of thyrotropin-releasing hormone by nanoconstructs58

Nasal delivery of neuroprotective drugs for stroke59

Transdermal drug delivery for neurological disorders59

Drug delivery to the brain via inner ear60

Invasive neurosurgical approaches60

Intraarterial drug delivery to the brain60

Direct injection into the CNS substance or CNS lesions61

Intraventricular injection of drugs61

Intrathecal drug delivery62

Retrograde delivery to the brain via the epidural venous system63

Devices for drug delivery to the CNS63

Strategies for drug delivery to the CNS across the BBB64

Increasing the permeability (opening) of the BBB65

Osmotic opening of the BBB65

Focal disruption of BBB by ultrasound65

Chemical opening of the BBB66

Cerebral vasodilatation to open the BBB66

Use of nitric oxide donors to open the BBB66

Manipulation of the sphingosine 1-phosphate receptor system67

Pharmacological strategies to facilitate transport across the BBB67

2B-Trans™ technology with specific carrier protein67

ABC afflux transporters and penetration of the BBB68

Carrier-mediated drug delivery across the BBB68

Glutathione transporters for drug delivery across the BBB69

Glycosylation Independent Lysosomal Targeting69

Inhibition of P-glycoprotein to enhance drug delivery across the BBB70

Modification of the drug to enhance its lipid solubility70

Monoclonal antibody fusion proteins71


Peptide-mediated transport across the BBB72

Prodrug bioconversion strategies and their CNS selectivity73

Role of the transferrin-receptor system in CNS drug delivery74

Transport of small molecules across the BBB74

Transport across the BBB by short chain oligoglycerolipids74

Transvascular delivery across the BBB75

Trojan horse approach75

Use of receptor-mediated transocytosis to cross the BBB76

Cell-based drug delivery to the CNS77

Activated T lymphocytes78

Microglial cells78

Neural stem cells78

Drug delivery to the CNS by using novel formulations78

Crystalline formulations78


Monoclonal antibodies80



Brain-targeted chemical delivery systems81

Nanotechnology-based drug delivery to CNS82

Nanoparticles for drug delivery across the BBB82

Penetration of BBB by nanoparticles coated with polysorbate 8083

NanoDel? technology for crossing the BBB83

Masking BBB-limiting characteristics by nanotechnology83

Peptide-nanoparticle conjugates for crossing the BBB83

Nanovesicles for transport across BBB84

Nanotechnology-based devices and implants for CNS84

Biochip implants for drug delivery to the CNS85

Controlled-release microchip85

Retinal implant chip85

Convection-enhanced delivery to the CNS85

Systemic administration of drugs for CNS effects86

Sustained and controlled release drug delivery to the CNS86

Fast dissolving oral selegiline88

Choice of the route of systemic delivery for effect on the CNS disorders88

Methods of delivery of biopharmaceuticals to the CNS89

Delivery of biopharmaceuticals across the BBB89

Methods of delivery of peptides for CNS disorders89

Challenges for delivery of peptides across the BBB90

Transnasal administration of neuropeptides90

Direct delivery of neuropeptides into the brain90

Alteration of properties of the BBB for delivery of peptides91

Molecular manipulations of peptides to facilitate transport into CNS91

CNS delivery of peptides via conjugation to biological carriers92

Delivery of conopeptides to the brain92

Delivery of neurotrophic factors to the nervous system92

Systemic administration of NTFs94

Delivery systems to facilitate crossing of the BBB by NTFs95

Use of microspheres for delivery of neurotrophic factors95

Intracerebroventricular injection96

Direct application of NTFs to the CNS96

Intrathecal administration97

Implants for delivery of neurotrophic factors97

Use of neurotrophic factor mimics97

Use of microorganisms for therapeutic entry into the brain99

Bacteriophages as CNS therapeutics99

Intracellular drug delivery in the brain99

Local factors in the brain affecting drug action100

Methods for testing drug delivery to the CNS100

Animal models for testing drug delivery100

Screening for drug-P-gp interaction at BBB100

4.Delivery of Cell, Gene and Antisense Therapies to the CNS101


Cell therapy of neurological disorders101

Methods for delivering cell therapies in CNS disorders101

Encapsulated cells102

Genetically modified stem cells for metachromatic leukodystrophy103

CNS neotissue implant103

CNS delivery of cells by catheters103

Subarachnoid delivery of stem cells104

Intravascular administration104

Gene therapy techniques for the nervous system105


Methods of gene transfer to the nervous system106

AAV vector mediated gene therapy for neurogenetic disorders107

Ideal vector for gene therapy of neurological disorders107

Promoters of gene transfer107

Routes of delivery of genes to the nervous system108

Direct injection into CNS108

Introduction of the genes into cerebral circulation109

Introduction of genes into cerebrospinal fluid109

Intravenous administration of vectors109

Delivery of gene therapy to the peripheral nervous system110

Cell-mediated gene therapy of neurological disorders110

Neuronal cells110

Neural stem cells and progenitor cells110


Cerebral endothelial cells111

Implantation of genetically modified encapsulated cells into the brain111

Genetically modified bone marrow cells111

Nanoparticles as non-viral vectors for CNS gene therapy112

Companies involved in cell/gene therapy of neurological disorders112

Antisense therapy of CNS disorders113

Delivery of antisense oligonucleotides to the CNS114

Delivery of oligonucleotides cross the BBB115

Cellular delivery systems for oligonucleotides115

High-flow microinfusion into the brain parenchyma116

Systemic administration of peptide nucleic acids116

Introduction of antisense compounds into the CSF Pathways116

Intrathecal administration of antisense compounds117

Intracerebroventricular administration of antisense oligonucleotides117

Nanoparticle-based delivery of antisense therapy to the CNS118

Methods of delivery of ribozymes118

Delivery aspects of RNAi therapy of CNS disorders119

Delivery of siRNA to the CNS119

Future drug delivery strategies applicable to the CNS119

5.Drug Delivery in the Treatment of CNS Disorders121

Parkinson's disease121

Drug delivery systems for Parkinson's disease122

Duodenal levodopa infusion124

Transdermal drug delivery for PD124

Transdermal dopamine agonists for Parkinson's disease124

Transdermal administration of other drugs for Parkinson's disease126

Intracerebral administration of GDNF126

Cell therapy for Parkinson's disease126

Human dopaminergic neurons for PD128

Graft survival-enhancing drugs128

Xenografting porcine fetal neurons128

Encapsulated cells for PD129

Stem cells for PD129

Engineered stem cells for drug delivery to the brain in PD131

Human retinal pigment epithelium cells for PD131

Delivery of cells for PD132

Gene therapy for Parkinson disease132


Techniques of gene therapy for PD133

Prospects of gene therapy for Parkinson's disease136

Companies developing gene therapy for PD137

RNAi therapy of Parkinson's disease137

Alzheimer disease138

Drug delivery for Alzheimer disease138

Blood-brain partitioning of an AMPA receptor modulator139

Clearing amyloid through the BBB139

Delivery of the passive antibody directly to the brain139

Delivery of thyrotropin-releasing hormone analogs by molecular packaging140

Intranasal delivery of nerve growth factor to the brain140

Nanoparticle-based drug delivery for Alzheimer's disease140

Perispinal etanercept141

Slow release implant of an AChE inhibitor141

Transdermal drug delivery in Alzheimer's disease141

Trojan-horse approach to prevent build-up of A? aggregates142

Cell and gene therapy for Alzheimer disease142

NGF gene therapy142

Neprilysin gene therapy143

RNAi therapy of Alzheimer's disease144

Huntington's disease144

Treatment of Huntington's disease144

Drug delivery in Huntington's disease145

Gene therapy of Huntington's disease145

Encapsulated genetically engineered cellular implants145

Viral vector mediated administration of neurotrophic factors145

RNAi therapeutics for the treatment of HD145

Amyotrophic lateral sclerosis146

Treatment of ALS146

Drug delivery in ALS146

Gene and antisense therapy of amyotrophic lateral sclerosis147

Neurotrophic factor gene therapies of ALS147

Antisense therapy of ALS149

RNAi therapy of amyotrophic lateral sclerosis149

Drug delivery for CNS involvement in Hunter syndrome149

Cerebrovascular disease150

Treatment of stroke150

Drug delivery in stroke151

Intraarterial administration of tissue plasminogen activator in stroke151

Drug delivery for prevention of restenosis of carotid arteries152

Modified NO donors153

In-stent restenosis153

Targeted local anti-restenotic drug delivery154

Catheter-based drug delivery for restenosis154

Stents for prevention of restenosis154

Drug-eluting stents155

Antisense approach to prevent restenosis156

Drug-eluting stents for the treatment of intracranial atherosclerosis156

Tissues transplants for stroke156

Transplant of encapsulated tissue secreting neurotrophic factors157

Cell therapy for stroke157

Stem cell transplant into the brain157

Immortalized cell grafts for stroke158

Intravenous infusion of marrow stromal cells158

Intravenous infusion of umbilical cord blood stem cells158

Future of cell therapy for stroke159

Gene therapy of cerebrovascular diseases159

Gene transfer to cerebral blood vessels159

NOS gene therapy for restenosis160

Gene therapy for cerebral ischemia161

Gene therapy of strokes with a genetic component163

Drug delivery to intracranial aneurysms163

Drug delivery for vasospasm following subarachnoid hemorrhage163

Intrathecal tissue plasminogen activator164

Gene therapy for vasospasm165

Drug delivery in multiple sclerosis166

An electronic device for self injection of interferon beta-1a166

Oral therapies for MS166

Antisense and RNAi approaches to MS167

Cell therapy for multiple sclerosis167

Hematopoietic stem cell transplantation for multiple sclerosis168

Embryonic stem cells and neural precursor cells for MS168

Gene therapy for multiple sclerosis168

Drug delivery in epilepsy169

Routes of administration of antiepileptic drugs169

Controlled-release preparations of carbamazepine169

Various methods of delivery of diazepam170

Methods of delivery of novel antiepileptic therapies170

Regulated activation of prodrugs170

Use of neuronal membrane transporter170

Delivery of the antiepileptic conopeptides to the brain171

Nasal administration of AEDs171

Intracerebral administration of phenytoin171

The role of drug delivery in status epilepticus172

Cell therapy of epilepsy172

Gene therapy for epilepsy173

Gene therapy for neuroprotection in epilepsy173

Concluding remarks on drug delivery in epilepsy174

Drug delivery for pain174

Intranasal delivery of analgesics175

Intranasal administration of morphine175

Intranasal fentanyl176

Intranasal buprenorphine177

Intranasal ketamine177

Delivery of analgesics by inhalation177

Spinal delivery of analgesics178

Epidural administration of encapsulated morphine180

Relief of pain by intrathecal ziconotide180

Intrathecal neostigmine180

Intrathecal prostaglandin antagonists181

Intrathecal non-NMDA antagonists181

Intrathecal siRNA for relief of neuropathic pain181

Intracerebroventricular drug delivery for pain181

Delivery of analgesics to the CNS across the BBB182

Drug delivery for migraine182

Management of migraine182

Novel drug delivery methods for migraine183

Nasal formulations for migraine184

Sublingual spray for migraine185

Needle-free drug delivery for migraine185

Relief of spasticity by intrathecal baclofen185

Drug delivery for brain tumors186

Methods for evaluation of anticancer drug penetration into brain tumor186

Innovative methods of drug delivery for glioblastoma multiforme186

Anticancer agents with increased penetration of BBB187

Local delivery of chemotherapeutic agents into the tumor187

Carmustine biodegradable polymer implants187

Fibrin glue implants containing anticancer drugs.188

Biodegradable microspheres containing 5-FU188

Nanoparticles for delivery of drugs to brain tumors across BBB189

Convection-enhanced delivery189

Delivery of antibody-based anticancer therapy by ultrasound BBB disruption190

Targeted monoclonal antibodies conjugated with liposomes190


Lipid-coated microbubbles as a delivery vehicle for taxol191

Thermoliposomes containing cytotoxic drugs191

Introduction of the chemotherapeutic agent into the CSF pathways191

Intrathecal chemotherapy191

Intraventricular chemotherapy for meningeal cancer191

Increasing the permeability of blood-tumor barrier to anticancer drugs192

Disruption of BBB192

Nanoparticle-based targeted delivery of chemotherapy across the BBB193

Modulating efflux transporters to enhance chemotherapy penetration193

PDE5 inhibitors for enhancing tumor permeability to chemotherapy194

Intraarterial chemotherapy194

Interstitial delivery of dexamethasone for reduction of peritumor edema195

Photodynamic therapy for chemosensitization195

Boron neutron capture therapy196

Gene therapy for glioblastoma multiforme.197

Single-chain antibody-targeted adenoviral vectors197

Peptides targeted to glial tumor cells198

Antiangiogenic gene therapy198

RNAi gene therapy of brain cancer199

Drug delivery for traumatic brain injury199

Cell therapy of traumatic brain injury199

Gene therapy for traumatic brain injury200

Drug delivery for spinal cord injury200

Administration of neurotrotrophic factors for spinal cord injury200

Cell therapy for spinal cord injury201

Transplantation of glial cells for SCI201

Fetal neural grafts for SCI201

Embryonic stem cells for SCI201

Schwann cell transplants for SCI202

Olfactory glial cells for SCI202

Marrow stromal cells for SCI203

Intravenous injection of stem cells for spinal cord repair203

Combinatorial approach for regeneration in SCI203

Cell therapy of syringomyelia203

Gene therapy of spinal cord injury204

Drug delivery for retinal disorders204

Age-related macular degeneration204

TheraSight ocular brachytherapy system for wet AMD205

Combretastatin A4P for myopic macular degeneration205

Gene therapy for AMD205

Anti-VEGF approach to AMD206

Delivery of aptamers for treatment of AMD206

Stem cell therapy for retinitis pigmentosa207

Proliferative retinopathies207

Drug delivery in CNS infections207

Drug delivery in neuroAIDS208

6.Markets for Drug Delivery in CNS Disorders209


Methods of calculation of CNS drug delivery markets209

Markets for CNS drug delivery technologies209

Drug delivery share in selected CNS markets210

CNS share of drug delivery technologies210

Geographical distribution of CNS drug delivery markets211

Impact of improved drug delivery on CNS drug markets211

Neurodegenerative disorders211

Alzheimer's disease211

Parkinson's Disease212

Huntington's disease212

Amyotrophic lateral sclerosis212


Migraine and other headaches213


Spinal cord injury214

Multiple sclerosis214

Brain tumors214

Limitations of the current drug delivery technologies for CNS214

Unmet needs in CNS drug delivery technologies215

Future strategies for expanding CNS drug delivery markets216

Education of neurologists216

Demonstration of the advantages of the newer methods of delivery216

Rescue of old products by novel drug delivery methods217

Facilitation of the approval process of new drugs217







Table 1 1: Landmarks in the development of drug delivery to the CNS17

Table 2 1: Proteins expressed at the neurovascular unit30

Table 2 2: Transporters that control penetration of molecules across the BBB34

Table 2 3: Enzymes that control the penetration of molecules across the BBB36

Table 2 4: Factors that increase the permeability of the BBB41

Table 2 5: Diseases that affect the BBB42

Table 3 1: Various methods of drug delivery to the central nervous system55

Table 3 2: Drugs available for intrathecal administration62

Table 3 3: Strategies for drug delivery to the CNS across the BBB65

Table 3 4: Specific inhibitors of P-glycoprotein in clinical development70

Table 3 5: Molecules attached to Trojan horses injected intravenously for CNS effect75

Table 3 6: Examples of controlled and sustained release drug delivery for CNS disorders87

Table 3 7: Novel methods of delivery of drugs for CNS disorders88

Table 3 8: Indications for the clinical applications of NTFs in neurologic disorders93

Table 3 9: Methods for delivery of neurotrophic factors to the CNS93

Table 4 1: Methods for delivering cell therapies in CNS disorders102

Table 4 2: Classification of methods of gene therapy105

Table 4 3: Methods of gene transfer as applied to neurologic disorders106

Table 4 4: Companies developing cell/gene therapies for CNS disorders112

Table 4 5: Methods of antisense delivery as applied to the CNS114

Table 5 1: Strategies for the treatment of Parkinson's disease121

Table 5 2: Drug delivery systems for Parkinson's disease123

Table 5 3: Types of cell used for investigative treatment of Parkinson's disease127

Table 5 4: Status of cell therapies in development for Parkinson's disease127

Table 5 5: Gene therapy techniques applicable to Parkinson disease133

Table 5 6: Companies developing gene therapy for Parkinson's disease137

Table 5 7: Classification of pharmacotherapy for Alzheimer disease138

Table 5 8: Novel drug delivery methods for Alzheimer disease therapies138

Table 5 9: Classification of neuroprotective agents for amyotrophic lateral sclerosis146

Table 5 10: Methods of delivery of therapies in development for ALS147

Table 5 11: Classification of treatments for stroke150

Table 5 12: Treatments of stroke involving innovative drug delivery methods151

Table 5 13: Drug delivery for prevention of carotid artery restenosis after angioplasty153

Table 5 14: Gene transfer in animal models of carotid artery restenosis160

Table 5 15: Neuroprotective gene transfer strategies in models of cerebral ischemia161

Table 5 16: Gene Therapy for reducing cerebral infarction in animal stroke models162

Table 5 17: Pharmacological agents for treatment of cerebral vasospasm163

Table 5 18: Gene therapy strategies for vasospasm165

Table 5 19: A classification of drug delivery methods used in management of pain175

Table 5 20: Spinal/intrathecal administration of drugs for pain178

Table 5 21: Investigational drugs for pain administered by intrathecal route178

Table 5 22: Current management of migraine182

Table 5 23: Novel drug delivery methods for migraine183

Table 5 24: Innovative methods of drug delivery for glioblastoma multiforme186

Table 5 25: Strategies for gene therapy of malignant brain tumors197

Table 6 1: Share of drug delivery technologies in selected CNS markets: 2009-2019210

Table 6 2: CNS market share of drug delivery technologies 2009-2019210

Table 6 3: Value of CNS drug delivery in the major world markets from 2009-2019211

Table 6 4: Limitations of the current drug delivery technologies for CNS215

Table 7 1: Collaborations of companies in CNS drug delivery295


Figure 1 1: Interaction of neurotransmitters with receptors20

Figure 2 1: The neurovascular unit29

Figure 2 2: Various forms of passage of substances across the blood brain barrier33

Figure 3 1: Routes of drug delivery to the brain56

Figure 3 2: Use of receptor-mediated transcytosis to cross the BBB76

Figure 5 1: Oral versus transdermal administration of a drug in Parkinson's disease125

Figure 5 2: Effect of tyrosine hydroxylase gene delivery on dopamine levels134

Figure 5 3: A concept of targeted drug delivery to GBM across the BBB193

Figure 6 1: Unmet needs in the CNS drug delivery technologies215

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