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Cardiovascular Drug Delivery - Technologies, Markets & Companies

  • ID: 4748177
  • Report
  • December 2019
  • Region: Global
  • 279 Pages
  • Jain PharmaBiotech
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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 the systemic administration of drugs for cardiovascular disorders are described including the 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.

The 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 a 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 the molecular pathophysiology of cardiovascular diseases have brought gene therapy within the realm of possibility as a novel approach to the 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 2018 to 2028 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 83 companies that either develop technologies for drug delivery to the cardiovascular system or products using these technologies are profiled and 80 collaborations between companies are tabulated. The bibliography includes 200 selected references from recent literature on this topic. The report is supplemented with 31 tables and 9 figures.

Report contains information on:

  • Cardiovascular diseases
  • Methods for drug delivery to the cardiovascular system
  • Cell therapy for cardiovascular disorders
  • Gene therapy for cardiovascular disorders
  • Drug-eluting stents
  • Markets for cardiovascular drug delivery
Note: Product cover images may vary from those shown
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0. Executive Summary  

1. Cardiovascular Diseases  
Introduction  
History of cardiovascular drug delivery  
Overview of cardiovascular disease  
Coronary artery disease
Angina pectoris
Myocardial infarction  
Limitations of current therapies for myocardial ischemic disease  
Cardiomyopathies  
Cardiac arrhythmias  
Congestive heart failure
Peripheral arterial disease
Current management  
Atherosclerosis  
The endothelium as a target for cardiovascular therapeutics
Molecular cardiology
Cardiogenomics  
Cardioproteomics
Personalized cardiology
Pharmacogenomics of cardiovascular disorders
Modifying the genetic risk for myocardial infarction  
Management of heart failure  
Management of hypertension  
Pharmacogenomics of diuretic drugs  
Pharmacogenomics of ACE inhibitors  
Management of hypertension by personalized approach
Pharmacogenetics of lipid-lowering therapies  
Polymorphisms in genes involved in cholesterol metabolism
Role of eNOS gene polymorphisms
Important advances in cardiovascular therapeutics  
Drug delivery, biotechnology and the cardiovascular system  
Role of cardiovascular imaging in cardiovascular therapeutics
Biologic therapeutics for cardiovascular disorders  
Chronopharmacotherapy of cardiovascular diseases  

2. Methods for Drug Delivery to the Cardiovascular System  
Introduction  
Routes of drug delivery to the cardiovascular system
Local administration of drugs to the cardiovascular system  
Intramyocardial drug delivery
Drug delivery via coronary venous system  
Intrapericardial drug delivery  
Formulations for drug delivery to the cardiovascular system  
Sustained and controlled release
Programming the release at a defined time  
Dosage formulation of calcium channel blockers  
Sustained and controlled release verapamil
Methods of administration of proteins and peptides  
Delivery of peptides by subcutaneous injection  
Depot formulations and implants  
Poly(ethylene glycol) technology
Liposomes for cardiovascular drug delivery  
Microencapsulation for protein delivery
Localized delivery of biomaterials for tissue engineering  
Oral delivery of proteins and peptides
Monoclonal antibodies for cardiovascular disorders  
Abciximab
Canakinumab  
PCSK9 MAbs
DDS to improve systemic delivery of cardiovascular drugs
Nanotechnology-based drug delivery
Controlled delivery of nanoparticles to injured vasculature  
Nanoparticles for cardiovascular imaging and targeted drug delivery  
Nanofiber-based scaffolds with drug-release properties  
Targeted drug delivery to the cardiovascular system  
Immunotargeting of liposomes to activated vascular endothelial cells  
PEGylated biodegradable particles targeted to inflamed endothelium
Devices for cardiovascular drug delivery  
Local drug delivery by catheters  
Microneedle for periarterial injection
Nanotechnology-based devices for the cardiovascular system
Liposomal nanodevices for targeted cardiovascular drug delivery  
Nanotechnology approach to the problem of “vulnerable plaque”  
Drug delivery in the management of cardiovascular disease  
Drug delivery in the management of hypertension  
Transnasal drug delivery for hypertension
Transdermal drug delivery for hypertension  
Oral extended and controlled release preparations for hypertension  
Long-acting hypertensives for 24 h blood pressure control  
Drug delivery to control early morning blood pressure peak  
Role of drug delivery in improving compliance with antihypertensive therapy  
Vaccines for hypertension  
Drug delivery in the treatment of angina pectoris
Sustained and controlled-release nitrate for angina pectoris  
Transdermal nitrate therapy
Controlled release calcium blockers for angina pectoris
Sustained-release formulation of ranolazine  
DDS in the management of ischemic heart disease  
Intravenous emulsified formulations of halogenated anesthetics  
Injectable peptide nanofibers for myocardial ischemia  
Delivery of angiogenesis-inducing agents for myocardial ischemia
Drug delivery for myocardial infarction  
Drug delivery for cardioprotection  
Cardioprotection during reperfusion  
Drug delivery for congestive heart failure
Oral human brain-type natriuretic peptide
Nitric oxide-based therapies for congestive heart failure  
Automated drug delivery system for cardiac failure  
Drug delivery for cardiac rhythm disorders
Drug delivery in the management of pulmonary hypertension  
Endothelin receptor antagonist treatment of PAH  
Prostacyclin by inhalation
Treprostinil  
Anticoagulation in cardiovascular disease
Oral heparin
Low molecular weight heparin-loaded polymeric nanoparticles
Transdermal anticoagulants  
Thrombolysis for cardiovascular disorders  
Use of ultrasound to facilitate thrombolysis  
Delivery of alteplase through the AngioJet rheolytic catheter  
Drug delivery for peripheral arterial disease  
Delivery of thrombolytic agent to the clot through a catheter  
Delivery of growth factors to promote angiogenesis in ischemic limbs
Immune modulation therapy for PAD
NO-based therapies for peripheral arterial disease  
Drug delivery in the management of hypercholesterolemia
Controlled/sustained release formulations of statins  
Combinations of statins with other drugs to increase efficacy  
Controlled release fenofibrate
Extended release nicotinic acid  
Intravenous infusion of lipoprotein preparations to raise HDL  
Innovative approaches to hypercholesterolemia
Therapeutic antagonism of ANGPTL3 gene  
Vaccines for lowering cholesterol by targeting PCSK9  
Single dose therapy for more than one cardiovascular disorder

3. Cell Therapy for Cardiovascular Disorders  
Introduction  
Inducing the proliferation of cardiomyocytes  
Role of stem cells in repair of the heart
Cell-mediated immune modulation for chronic heart disease  
Cell therapy for atherosclerotic coronary artery disease  
Transplantation of myoblasts for myocardial infarction
MyoCell™ (Bioheart)
Transplantation of cardiac progenitor cells for revascularization of myocardium  
Methods of delivery of cells to the heart  
Cellular cardiomyoplasty
IGF-1 delivery by nanofibers to improve cell therapy for MI
Intracoronary infusion of bone marrow-derived cells for AMI  
Non-invasive delivery of cells to the heart by Morph®guide catheter  
Transplantation of stem cells for myocardial infarction
Transplantation of embryonic stem cells  
Transplantation of hematopoietic stem cells  
Transplantation of cord blood stem cells for myocardial infarction  
Intracoronary infusion of mobilized peripheral blood stem cells
Human mesenchymal stem cells for cardiac regeneration
Cytokine preconditioning of human fetal liver CD133+ SCs  
Transplantation of expanded adult SCs derived from the heart  
Transplantation of endothelial cells
Transplantation of genetically modified cells  
Transplantation of cells secreting vascular endothelial growth factor  
Transplantation of genetically modified bone marrow stem cells
Cell transplantation for congestive heart failure  
Injection of adult stem cells for congestive heart failure
Intracoronary infusion of cardiac stem cells
Myoblasts for treatment of congestive heart failure  
Role of cell therapy in cardiac arrhythmias  
Atrioventricular conduction block  
Ventricular tachycardia  
ESCs for correction of congenital heart defects  
Cardiac progenitors cells for treatment of heart disease in children  
Stem cell therapy for peripheral arterial disease  
Targeted delivery of endothelial progenitor cells labeled with nanoparticles  
Clinical trials of cell therapy in cardiovascular disease
A critical evaluation of cell therapy for heart disease  
Publications of clinical trials of cell therapy for CVD  
Future directions for cell therapy of CVD  
Prospects of adult stem cell therapy for repair of heart  
Regeneration of cardiomyocytes without use of cardiac stem cells
Repair of the damaged heart

4. Gene Therapy for Cardiovascular Disorders  
Introduction  
Techniques of gene transfer to the cardiovascular system  
Direct plasmid injection into the myocardium  
Catheter-based systems for vector delivery
Ultrasound microbubbles for cardiovascular gene delivery
Vectors for cardiovascular gene therapy  
AAV vectors for therapeutic delivery to the heart  
Adenoviral vectors for cardiovascular diseases
Plasmid DNA-based delivery in cardiovascular disorders
Hypoxia-regulated gene therapy for myocardial ischemia
Angiogenesis and gene therapy of ischemic disorders  
Therapeutic angiogenesis vs. vascular growth factor therapy
Gene painting for delivery of targeted gene therapy to the heart  
Gene delivery to vascular endothelium  
Overexpression of eNOS to improve vasodilation with Ad vectors
Targeted plasmid DNA delivery to the cardiovascular system with nanoparticles  
Gene therapy for genetic cardiovascular disorders  
Genetic disorders predisposing to atherosclerosis
Familial hypercholesterolemia
Apolipoprotein E deficiency
Hypertension
Genetic factors for myocardial infarction  
Acquired cardiovascular diseases  
Coronary artery disease with angina pectoris
Ad5FGF-4  
Ischemic heart disease with myocardial infarction
Angiogenesis for cardiovascular disease
Myocardial repair with IGF-1 therapy
miRNA gene therapy for ischemic heart disease
Congestive heart failure
Rationale of gene therapy in CHF  
AAV-mediated gene transfer for CHF  
AngioCell gene therapy for CHF  
β-ARKct gene therapy  
Elevating cardiac dATP by gene therapy to improve cardiac function
Intracoronary adenovirus-mediated gene therapy for CHF
nNOS gene transfer in CHF  
Gene therapy for cardiac arrhythmias
Gene transfer for biological pacemakers  
Management of arrhythmias due to myoblast transplantation  
Genetically engineered cells as biological pacemakers  
Cholesterol reduction by genetic engineering of PCSK9 gene  
Gene therapy and heart transplantation
Gene therapy for peripheral arterial disease  
Angiogenesis by gene therapy  
HIF-1 gene therapy for peripheral arterial disease
HGF gene therapy for peripheral arterial disease
Ischemic neuropathy secondary to peripheral arterial disease
Maintaining vascular patency after surgery  
Antisense therapy for cardiovascular disorders  
Antisense therapy for hypertension  
Antisense therapy for hypercholesterolemia  
Mipomersen  
Antisense oligonucleotides targeting ANGPTL3
Antisense drugs targeting PCSK9  
RNAi for cardiovascular disorders
RNAi for hypercholesterolemia
siRNAs targeting PCSK9
microRNA and the cardiovascular system
Role of miRNAs in angiogenesis  
Role of miRNAs in cardiac hypertrophy and failure  
Role of miRNAs in conduction and rhythm disorders of the heart
miRNA-based approach for reduction of hypercholesterolemia  
miRNAs as therapeutic targets for cardiovascular diseases  
Future prospects of miRNA in the cardiovascular therapeutics
Future prospects of gene therapy of cardiovascular disorders
Companies involved in gene therapy of cardiovascular disorders  

5. Drug-Eluting Stents  
Introduction  
Percutaneous transluminal coronary angioplasty  
Stents  
Restenosis  
Pathomechanism  
Treatment
Nitric oxide-based therapies for restenosis  
Carbon monoxide inhalation for preventing restenosis  
Antisense approaches for prevention of restenosis after angioplasty
Gene therapy to prevent restenosis after angioplasty  
Delivery of gene therapy for restenosis
HSV-1 gene therapy to prevent intimal hyperplasia
miRNA-based gene therapy for restenosis following angioplasty
Nonviral gene therapy to prevent intimal hyperplasia  
NOS gene therapy for restenosis
Targets for gene therapy of restenosis
Viral vector-mediated gene therapy for restenosis
Drug delivery devices for restenosis  
Local drug delivery by catheter  
Stenosis associated with stents
Absorbable metal stents  
Drug-eluting stents
Various types of DES
CYPHER® sirolimus-eluting coronary stent
Dexamethasone-eluting stents  
NO-generating stents  
Paclitaxel-eluting stents
Sirolimus-eluting vs paclitaxel-eluting stents  
Novel technologies for DES  
Bio-absorbable DES
Drug-eluting stents coated with polymer surfaces  
Endeavour DES
Polymer-free drug-coated stent for patients at high risk of bleeding  
Stents for delivery of gene therapy  
Stem cell-based stents  
VAN 10-4 DES  
Nanotechnology-based stents
Drugs encapsulated in biodegradable nanoparticles
Magnetic nanoparticle-coated DES  
Magnetic nanoparticles encapsulating paclitaxel targeted to stents
Nanocoated DES
Nanopores to enhance compatibility of DES
Paclitaxel-encapsulated targeted lipid-polymeric nanoparticles
The ideal DES
Companies developing drug-eluting stents  
Clinical trials of drug-eluting stents  
Measurements used in clinical trials of DES  
TAXUS paclitaxel-eluting stents  
XIENCE™ V everolimus-eluting coronary stent
COSTAR II clinical trial
Endeavor RESOLUTE zotarolimus-eluting stent system  
CUSTOM I clinical trial  
NOBORI CORE Trial
LEADERS trial
Comparison of DES releasing either zotarolimus or everolimus  
Comparison of DES versus bare metal stents in clinical trials
Biosorbable vs drug-eluting metallic stents  
Multi-Link Vision bare metal stent vs DES  
Guidelines for DES vs BMS
DES vs BMS for off-label indications  
Role of DES in cases of bare-metal in-stent restenosis
Comparison of revascularization methods for stable coronary disease
DES versus coronary artery bypass graft  
DES versus balloon catheter coated with paclitaxel  
DES versus intracoronary radiation therapy for recurrent stenosis
PCI plus DES as the preferred method for treatment of MI  
Cost-effectiveness of DES  
Safety issues of DES  
Adverse reactions to DES
Long-term safety studies of DES
Endothelial vascular dysfunction due to sirolismus  
Risk of clotting with DES
Effect of blood clot on release of drug from DES  
Measures to prevent clotting associated with DES  
Clopidogrel use and long-term outcomes of patients receiving DES  
Cangrelor for platelet inhibition to prevent stent thrombosis
Prasugrel as antiplatelet agent
Use of magnetized cell lining to prevent clotting of DES
Regulatory issues of DES  
Approved drug-eluting stents  
Safety issues of drug-eluting stents
Assesssment of efficacy of various drug-eluting stents
Future prospects of treatment of restenosis by DES  
Effect of stent cost on clinical applications
Future role of DES in the management of cardiovascular diseases
Improvements in stent technology  
Bioabsorbale stent  
DES vs drug-eluting balloons

6. Markets for Cardiovascular Drug Delivery
Introduction  
Epidemiology of cardiovascular disease
Cost of care of cardiovascular disorders  
Cardiovascular markets according to important diseases  
Antithrombotics  
Anticholesterol agents  
Antihypertensive agents  
Drugs for congestive heart failure  
Markets for innovative technologies for cardiovascular disorders  
Markets for cell therapy of cardiovascular disorders
Markets for gene therapy of cardiovascular disorders  
Markets for drug-eluting stents
Major players in DES market  
Impact of safety issues on future markets for DES  
DES market in Asia  
Patenting and legal issues of DES  
The financial impact of DES on cardiovascular markets  
Unmet needs for cardiovascular drug delivery
Role of DDS in developing cardiovascular markets  
Markets for cardiovascular devices  
Marketing of innovative cardiovascular drug delivery devices
Direct to consumer advertising of DES
Future trends in the integration of drug delivery with therapeutics  
Future of cardiovascular drug delivery  

7. Companies involved in Cardiovascular Drug Delivery  
Profiles of companies
Collaborations

8. References

Tables
Table 1-1: Landmarks in the historical evolution of cardiovascular drug delivery
Table 1-2: Approaches to management of myocardial infarction and its sequele  
Table 1-3: Gene polymorphisms that alter cardiovascular response to drugs  
Table 2-1: Routes of drug delivery used for treatment of cardiovascular disorders  
Table 2-2: Formulations for drug delivery to the cardiovascular system
Table 2-3: Monoclonal antibodies used for cardiovascular disorders  
Table 2-4: Improved methods of systemic drug delivery of cardiovascular drugs  
Table 2-5: Targeted delivery of therapeutic substances to the cardiovascular system  
Table 2-6: Classification of devices for drug delivery to the cardiovascular system
Table 2-7: Various methods of delivery of therapeutic agents for hypertension
Table 2-8: Marketed controlled/ extended release preparation for hypertension
Table 2-9: Methods of delivery of nitrate therapy in angina pectoris
Table 2-10: Drug delivery in ischemic heart disease
Table 2-11: Strategies for cardioprotection  
Table 2-12: Drug delivery for peripheral arterial disorders  
Table 3-1: Clinical trials of cell therapy in cardiovascular disease
Table 4-1: Cardiovascular disorders for which gene therapy is being considered.  
Table 4-2: Catheter-based systems for vector delivery to the cardiovascular system
Table 4-3: Potential applications of antisense in cardiovascular disorders
Table 4-4: Companies involved in gene therapy of cardiovascular diseases  
Table 5-1: Treatment of restenosis  
Table 5-2: Devices used for drug delivery in restenosis  
Table 5-3: Companies involved in drug-eluting stents  
Table 5-4: Drug-eluting stents approved by the FDA
Table 6-1: Prevalence of cardiovascular disorders in major markets: US 2018-2028  
Table 6-2: Prevalence of cardiovascular disorders in major markets: Europe 2018-2028
Table 6-3: Prevalence of cardiovascular disorders in major markets: Japan 2018-2028  
Table 6-4: Values of cardiovascular DDS in major markets 2018-2028  
Table 6-5: Markets for innovative technologies for cardiovascular disorders 2018-2028
Table 7-1: Top 5 companies in cardiovascular drug delivery
Table 7-2: Collaborations in cardiovascular drug delivery

Figures
Figure 1-1: Drug delivery, biotechnology and cardiovascular diseases  
Figure 2-1: MicroSyringe for periarterial injection  
Figure 2-2: Patch for delivery of follistatin-like 1 factor for myocardial infarction  
Figure 2-3: Lipoprotein metabolism in ANGPTL3 deficiency  
Figure 5-1: Vicious circle of vascular occlusion following angioplasty and stenting
Figure 5-2: Measurement of in-stent stenosis
Figure 5-3: Medtronic’s Endeavour drug-eluting stent
Figure 5-4: Magnetic nanoparticle-coated stent  
Figure 6-1: Unmet needs for cardiovascular drug delivery
Abbreviations
ACE angiotensin-converting-enzyme
CAD coronary artery disease
CHF congestive heart failure
CR controlled release
CVS cardiovascular system
DDS drug delivery system
DES drug-eluting stent
eNOS endothelial nitric oxide synthase
EPC endothelial progenitor cells
HDL high-density lipoprotein
hESCs human embryonic stem cells
HSCs hematopoietic stem cells
IHD ischemic heart disease
LDL low-density lipoprotein
NIH Nation Institutes of Health, USA
NO nitric oxide
NOS nitric oxide synthase
PAD peripheral arterial disease
PEG poly(ethylene glycol
PTCA percutaneous transluminal coronary angioplasty
RNAi RNA interference
SC stem cell
siRNA short interfering RNAs
VEGF vascular endothelial growth factor

Note: Product cover images may vary from those shown
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