Reportlinker Adds Cardiovascular Drug Delivery - technologies, markets and companies

Monday, June 7, 2010 General News
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NEW YORK, June 7 announces that a new market research report is available in its catalogue:

Cardiovascular Drug Delivery - technologies, markets and companies


Drug delivery to the cardiovascular system is different from delivery to other systems because of the anatomy and physiology of the vascular system; it supplies blood and nutrients to all organs of the body. Drugs can be introduced into the vascular system for systemic effects or targeted to an organ via the regional blood supply. In addition to the usual formulations of drugs such as controlled release, devices are used as well. This report starts with an introduction to molecular cardiology and discusses its relationship to biotechnology and drug delivery systems.

Drug delivery to the cardiovascular system is approached at three levels: (1) routes of drug delivery; (2) formulations; and finally (3) applications to various diseases. Formulations for drug delivery to the cardiovascular system range from controlled release preparations to delivery of proteins and peptides. Cell and gene therapies, including antisense and RNA interference, are described in full chapters as they are the most innovative methods of delivery of therapeutics. Various methods of improving systemic administration of drugs for cardiovascular disorders are described including use of nanotechnology.

Cell-selective targeted drug delivery has emerged as one of the most significant areas of biomedical engineering research, to optimize the therapeutic efficacy of a drug by strictly localizing its pharmacological activity to a pathophysiologically relevant tissue system. These concepts have been applied to targeted drug delivery to the cardiovascular system. Devices for drug delivery to the cardiovascular system are also described.

Role of drug delivery in various cardiovascular disorders such as myocardial ischemia, hypertension and hypercholesterolemia is discussed. Cardioprotection is also discussed. Some of the preparations and technologies are also applicable to peripheral arterial diseases. Controlled release systems are based on chronopharmacology, which deals with the effects of circadian biological rhythms on drug actions. A full chapter is devoted to drug-eluting stents as treatment for restenosis following stenting of coronary arteries. Fifteen companies are involved in drug-eluting stents.

New cell-based therapeutic strategies are being developed in response to the shortcomings of available treatments for heart disease. Potential repair by cell grafting or mobilizing endogenous cells holds particular attraction in heart disease, where the meager capacity for cardiomyocyte proliferation likely contributes to the irreversibility of heart failure. Cell therapy approaches include attempts to reinitiate cardiomyocyte proliferation in the adult, conversion of fibroblasts to contractile myocytes, conversion of bone marrow stem cells into cardiomyocytes, and transplantation of myocytes or other cells into injured myocardium.

Advances in molecular pathophysiology of cardiovascular diseases have brought gene therapy within the realm of possibility as a novel approach to treatment of these diseases. It is hoped that gene therapy will be less expensive and affordable because the techniques involved are simpler than those involved in cardiac bypass surgery, heart transplantation and stent implantation. Gene therapy would be a more physiologic approach to deliver vasoprotective molecules to the site of vascular lesion. Gene therapy is not only a sophisticated method of drug delivery; it may at time need drug delivery devices such as catheters for transfer of genes to various parts of the cardiovascular system.

The cardiovascular drug delivery markets are estimated for the years 2009 to 2019 on the basis of epidemiology and total markets for cardiovascular therapeutics. The estimates take into consideration the anticipated advances and availability of various technologies, particularly drug delivery devices in the future. Markets for drug-eluting stents are calculated separately. Role of drug delivery in developing cardiovascular markets is defined and unmet needs in cardiovascular drug delivery technologies are identified.

Selected 95 companies that either develop technologies for drug delivery to the cardiovascular system or products using these technologies are profiled and 72 collaborations between companies are tabulated. The bibliography includes 200 selected references from recent literature on this topic. The report is supplemented with 27 tables and 6 figures


0.Executive Summary11

1.Cardiovascular Diseases13


History of cardiovascular drug delivery13

Overview of cardiovascular disease14

Coronary artery disease14

Angina pectoris14

Limitations of current therapies for myocardial ischemic disease14


Cardiac arrhythmias15

Congestive heart failure15

Peripheral arterial disease15

Current management16


The endothelium as a target for cardiovascular therapeutics16

Molecular cardiology17



Personalized cardiology18

Pharmacogenomics of cardiovascular disorders18

Modifying the genetic risk for myocardial infarction19

Management of heart failure19

Management of hypertension20

Pharmacogenomics of diuretic drugs20

Pharmacogenomics of ACE inhibitors20

Management of hypertension by personalized approach21

Pharmacogenetics of lipid-lowering therapies21

Polymorphisms in genes involved in cholesterol metabolism21

Role of eNOS gene polymorphisms22

Important advances in cardiovascular therapeutics22

Drug delivery, biotechnology and the cardiovascular system23

Role of cardiovascular imaging in cardiovascular therapeutics23

Chronopharmacotherapy of cardiovascular diseases23

2.Methods for Drug Delivery to the Cardiovascular System25


Routes of drug delivery to the cardiovascular system25

Local administration of drugs to the cardiovascular system25

Intramyocardial drug delivery25

Drug delivery via coronary venous system26

Intrapericardial drug delivery26

Formulations for drug delivery to the cardiovascular system26

Sustained and controlled release27

Programming the release at a defined time27

Dosage formulation of calcium channel blockers28

Sustained and controlled release verapamil28

Methods of administration of proteins and peptides28

Delivery of peptides by subcutaneous injection29

Depot formulations and implants29

Poly(ethylene glycol) technology29

Microencapsulation for protein delivery30

Localized delivery of biomaterials for tissue engineering30

Oral delivery of proteins and peptides30

DDS to improve systemic delivery of cardiovascular drugs31

Nanotechnology-based drug delivery32

Controlled delivery of nanoparticles to injured vasculature33

Nanoparticles for cardiovascular imaging and targeted drug delivery34

Nanofiber-based scaffolds with drug-release properties34

Targeted drug delivery to the cardiovascular system34

Immunotargeting of liposomes to activated vascular endothelial cells35

PEGylated biodegradable particles targeted to inflamed endothelium36

Devices for cardiovascular drug delivery36

Local drug delivery by catheters37

Microneedle for periarterial injection38

Nanotechnology-based devices for the cardiovascular system38

Liposomal nanodevices for targeted cardiovascular drug delivery39

Nanotechnology approach to the problem of "vulnerable plaque"39

Drug delivery in the management of cardiovascular disease40

Drug delivery in the management of hypertension40

Transnasal drug delivery for hypertension40

Transdermal drug delivery for hypertension41

Oral extended and controlled release preparations for hypertension41

Long-acting hypertensives for 24 h blood pressure control42

Drug delivery to control early morning blood pressure peak42

Role of drug delivery in improving compliance with antihypertensive therapy43

Drug delivery for congestive heart failure43

Oral human brain-type natriuretic peptide43

Nitric oxide-based therapies for congestive heart failure43

Automated drug delivery system for cardiac failure44

DDS in the management of ischemic heart disease44

Intravenous emulsified formulations of halogenated anesthetics45

Injectable peptide nanofibers for myocardial ischemia45

Delivery of angiogenesis-inducing agents for myocardial ischemia45

Drug delivery for cardioprotection46

Drug delivery for cardiac rhythm disorders47

Drug delivery in the treatment of angina pectoris48

Sustained and controlled-release nitrate for angina pectoris48

Transdermal nitrate therapy48

Controlled release calcium blockers for angina pectoris49

Vaccines for hypertension50

Drug delivery in the management of pulmonary hypertension50

Prostacyclin by inhalation51

Endothelin receptor antagonist treatment of PAH51

Anticoagulation in cardiovascular disease51

Oral heparin51

Low molecular weight heparin-loaded polymeric nanoparticles52

Transdermal anticoagulants52

Thrombolysis for cardiovascular disorders52

Use of ultrasound to facilitate thrombolysis52

Delivery of alteplase through the AngioJet rheolytic catheter53

Drug delivery for peripheral arterial disease53

Delivery of thrombolytic agent to the clot through a catheter53

Delivery of growth factors to promote angiogenesis in ischemic limbs54

Immune modulation therapy for PAD54

NO-based therapies for peripheral arterial disease54

Drug delivery in the management of hypercholesterolemia55

Controlled/sustained release formulations of statins55

Combinations of statins with other drugs to increase efficacy55

Controlled release fenofibrate56

Extended release nicotinic acid57

Intravenous infusion of lipoprotein preparations to raise HDL57

Innovative approaches to hypercholesterolemia58

Single dose therapy for more than one cardiovascular disorder58

3.Cell Therapy for Cardiovascular Disorders61


Inducing the proliferation of cardiomyocytes61

Role of stem cells in repair of the heart61

Cell-mediated immune modulation for chronic heart disease61

Cell therapy for atherosclerotic coronary artery disease62

Transplantation of myoblasts for myocardial infarction62

MyoCell(TM) (Bioheart)63

Transplantation of cardiac progenitor cells for revascularization of myocardium64

Methods of delivery of cells to the heart64

Cellular cardiomyoplasty64

IGF-1 delivery by nanofibers to improve cell therapy for MI65

Intracoronary infusion of bone marrow-derived cells for AMI65

Non-invasive delivery of cells to the heart by Morph®guide catheter65

Transplantation of stem cells for myocardial infarction66

Transplantation of embryonic stem cells66

Transplantation of hematopoietic stem cells66

Transplantation of cord blood stem cells for myocardial infarction66

Intracoronary infusion of mobilized peripheral blood stem cells67

Human mesenchymal stem cells for cardiac regeneration67

Cytokine preconditioning of human fetal liver CD133+ SCs68

Transplantation of expanded adult SCs derived from the heart68

Transplantation of endothelial cells68

Transplantation of genetically modified cells69

Transplantation of cells secreting vascular endothelial growth factor69

Transplantation of genetically modified bone marrow stem cells69

Cell transplantation for congestive heart failure69

Myoblasts for treatment of congestive heart failure69

Injection of adult stem cells for congestive heart failure70

Role of cell therapy in cardiac arrhythmias70

Atrioventricular conduction block71

Ventricular tachycardia71

ESCs for correction of congenital heart defects72

Cardiac progenitors cells for treatment of heart disease in children72

Stem cell therapy for peripheral arterial disease72

Targeted delivery of endothelial progenitor cells labeled with nanoparticles73

Clinical trials of cell therapy in cardiovascular disease73

A critical evaluation of cell therapy for heart disease75

Publications of clinical trials of cell therapy for CVD75

Future directions for cell therapy of CVD76

4.Gene Therapy for Cardiovascular Disorders79


Techniques of gene transfer to the cardiovascular system80

Direct plasmid injection into the myocardium80

Catheter-based systems for vector delivery80

Ultrasound microbubbles for cardiovascular gene delivery81

Vectors for cardiovascular gene therapy81

Adenoviral vectors for cardiovascular diseases81

Plasmid DNA-based delivery in cardiovascular disorders82

Intravenous rAAV vectors for targeted delivery to the heart82

Hypoxia-regulated gene therapy for myocardial ischemia82

Angiogenesis and gene therapy of ischemic disorders83

Therapeutic angiogenesis vs. vascular growth factor therapy83

Gene painting for delivery of targeted gene therapy to the heart84

Gene delivery to vascular endothelium84

Targeted plasmid DNA delivery to the cardiovascular system with nanoparticles84

Gene delivery by vascular stents85

Gene therapy for genetic cardiovascular disorders85

Genetic disorders predisposing to atherosclerosis85

Familial hypercholesterolemia86

Apolipoprotein E deficiency87


Genetic factors for myocardial infarction88

Acquired cardiovascular diseases88

Coronary artery disease with angina pectoris89


Ischemic heart disease with myocardial infarction89

Angiogenesis for cardiovascular disease90

Myocardial repair with IGF-1 therapy90

Congestive heart failure91

Rationale of gene therapy in CHF91

-ARKct gene therapy91

Intracoronary adenovirus-mediated gene therapy for CHF92

AAV-mediated gene transfer for CHF92

AngioCell gene therapy for CHF92

nNOS gene transfer in CHF93

Gene therapy for cardiac arrhythmias93

Gene transfer for biological pacemakers93

Management of arrhythmias due to myoblast transplantation94

Genetically engineered cells as biological pacemakers95

Gene therapy and heart transplantation95

Gene therapy for peripheral arterial disease96

Angiogenesis by gene therapy96

HIF-1? gene therapy for peripheral arterial disease96

HGF gene therapy for peripheral arterial disease97

Ischemic neuropathy secondary to peripheral arterial disease97

Maintaining vascular patency after surgery97

Antisense therapy for cardiovascular disorders98

Antisense therapy for hypertension98

Antisense therapy for hypercholesterolemia99

RNAi for cardiovascular disorders99

RNAi for hypercholesterolemia100

microRNA and the cardiovascular system101

Role of miRNAs in angiogenesis101

Role of miRNAs in cardiac hypertrophy and failure101

Role of miRNAs in conduction and rhythm disorders of the heart102

miRNA-based approach for reduction of hypercholesterolemia102

miRNAs as therapeutic targets for cardiovascular diseases102

Future prospects of miRNA in the cardiovascular therapeutics103

Future prospects of gene therapy of cardiovascular disorders103

Companies involved in gene therapy of cardiovascular disorders104

5.Drug-Eluting Stents105


Percutaneous transluminal coronary angioplasty105





Nitric oxide-based therapies for restenosis106

Carbon monoxide inhalation for preventing restenosis107

Antisense approaches for prevention of restenosis after angioplasty107

miRNA-based approach for restenosis following angioplasty109

Gene therapy to prevent restenosis after angioplasty109

Techniques of gene therapy for restenosis110

NOS gene therapy for restenosis111

Non-viral gene therapy to prevent intimal hyperplasia111

HSV-1 gene therapy to prevent intimal hyperplasia111

Drug delivery devices for restenosis112

Local drug delivery by catheter112

Absorbable metal stents113

Drug-eluting stents113

Various types of DES113

CYPHER® sirolimus-eluting coronary stent113

Sirolimus-eluting vs paclitaxel-eluting stents114

Paclitaxel-eluting stents114

Dexamethasone-eluting stents115

NO-generating stents115

Dexamethasone-eluting stents116

Novel technologies for DES116

Stents for delivery of gene therapy116

Stem cell-based stents116

Drug-eluting stents coated with polymer surfaces117

Absorbable DES117

Endeavour DES117

Bio-absorbable low-dose DES118

VAN 10-4 DES119

Nanotechnology-based stents119

Drugs encapsulated in biodegradable nanoparticles119

Magnetic nanoparticle-coated DES119

Nanocoated DES120

Nanopores to enhance compatibility of DES121

The ideal DES121

Companies developing drug-eluting stents121

Clinical trials of drug-eluting stents122

Measurements used in clinical trials of DES122

TAXUS paclitaxel-eluting stents123

XIENCE(TM) V everolimus-eluting coronary stent124

COSTAR II clinical trial125

Endeavor RESOLUTE zotarolimus-eluting stent system125

CUSTOM I clinical trial126


LEADERS trial126

Comparison of DES in clinical trials127

Comparison of DES with competing technologies127

DES versus coronary artery bypass graft127

DES versus bare metal stents128

Guidelines for DES vs BMS130

DES vs BMS for off-label indications131

Role of DES in cases of bare-metal in-stent restenosis131

DES versus balloon catheter coated with paclitaxel131

DES versus intracoronary radiation therapy for recurrent stenosis132

Cost-effectiveness of DES132

Safety issues of DES133

Adverse reactions to DES133

Endothelial vascular dysfunction due to sirolismus133

Risk of clotting with DES133

Clopidogrel use and long-term outcomes of patients receiving DES135

Effect of blood clot on release of drug from DES135

Use of magnetized cell lining to prevent clotting of DES136

Long-term safety studies of DES136

Regulatory issues of DES137

Future prospects for treatment of restenosis by DES138

Future role of DES in management of cardiovascular diseases138

Stent cost and marketing strategies139

Improvements in stent technology139

Bioabsorbale stent140

6.Markets for Cardiovascular Drug Delivery141


Epidemiology of cardiovascular disease141

Cost of care of cardiovascular disorders142

Cardiovascular markets according to important diseases143


Anticholesterol agents143

Antihypertensive agents144

Drugs for congestive heart failure144

Markets for innovative technologies for cardiovascular disorders144

Markets for cell therapy of cardiovascular disorders144

Markets for gene therapy of cardiovascular disorders145

Markets for drug-eluting stents145

Major players in DES market145

Impact of safety issues on future markets for DES145

DES market in Asia146

Patenting and legal issues of DES147

The financial impact of DES on cardiovascular markets147

Unmet needs for cardiovascular drug delivery148

Role of DDS in developing cardiovascular markets149

Markets for cardiovascular devices149

Marketing of innovative cardiovascular drug delivery devices149

Direct to consumer advertising of DES150

Future trends in the integration of drug delivery with therapeutics150

Future prospects of cardiovascular drug delivery150

7.Companies involved in Cardiovascular Drug Delivery153

Profiles of companies153




Table 1 1: Landmarks in the historical evolution of cardiovascular drug delivery13

Table 1 2: Gene polymorphisms that alter cardiovascular response to drugs18

Table 2 1: Routes of drug delivery used for treatment of cardiovascular disorders25

Table 2 2: Formulations for drug delivery to the cardiovascular system26

Table 2 3: Improved methods of systemic drug delivery of cardiovascular drugs32

Table 2 4: Targeted delivery of therapeutic substances to the cardiovascular system35

Table 2 5: Classification of devices for drug delivery to the cardiovascular system36

Table 2 6: Various methods of delivery of therapeutic agents for hypertension40

Table 2 7: Marketed controlled/ extended release preparation for hypertension42

Table 2 8: Drug delivery in ischemic heart disease44

Table 2 9: Methods of delivery of nitrate therapy in angina pectoris48

Table 2 10: Drug delivery for peripheral arterial disorders53

Table 3 1: Clinical trials of cell therapy in cardiovascular disease73

Table 4 1: Cardiovascular disorders for which gene therapy is being considered.79

Table 4 2: Catheter-based systems for vector delivery to the cardiovascular system80

Table 4 3: Potential applications of antisense in cardiovascular disorders98

Table 4 4: Companies involved in gene therapy of cardiovascular diseases104

Table 5 1: Treatment of restenosis106

Table 5 2: Devices used for drug delivery in restenosis112

Table 5 3: Companies involved in drug-eluting stents122

Table 6 1: Prevalence of cardiovascular disorders in major markets: US 2009-2019142

Table 6 2: Prevalence of cardiovascular disorders in major markets: Europe 2009-2019142

Table 6 3: Prevalence of cardiovascular disorders in major markets: Japan 2009-2019142

Table 6 4: Values of cardiovascular DDS in major markets 2009-2019143

Table 6 5: Markets for innovative technologies for cardiovascular disorders 2009-2019144

Table 7 1: Top 5 companies in cardiovascular drug delivery153

Table 7 2: Collaborations in cardiovascular drug delivery255


Figure 1 1: Drug delivery, biotechnology and cardiovascular diseases23

Figure 2 1: Microneedle for periarterial injection38

Figure 5 1: Vicious circle of vascular occlusion following angioplasty and stenting107

Figure 5 2: Medtronic's Endeavour drug-eluting stent118

Figure 5 3: Magnetic nanoparticle-coated stent120

Figure 6 1: Unmet needs for cardiovascular drug delivery148

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Drug Delivery Technology Industry: Cardiovascular Drug Delivery - technologies,markets and companies

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Nicolas Bombourg Reportlinker Email: US: (805)652-2626 Intl: +1 805-652-2626

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