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Cardiovascular Drug Delivery - Technologies, Markets and Companies Product Image

Cardiovascular Drug Delivery - Technologies, Markets and Companies

  • Published: April 2014
  • Region: Global
  • 270 Pages
  • Jain PharmaBiotech

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.

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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
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
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
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
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
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 cardioprotection
Cardioprotection during reperfusion
Drug delivery for cardiac rhythm disorders
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
Vaccines for hypertension
Drug delivery in the management of pulmonary hypertension
Prostacyclin by inhalation
Endothelin receptor antagonist treatment of PAH
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
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
ß-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
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
RNAi for cardiovascular disorders
RNAi for hypercholesterolemia
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
miRNA-based approach for restenosis following angioplasty
Gene therapy to prevent restenosis after angioplasty
Viral vector-mediated gene therapy for restenosis
Delivery of gene therapy for restenosis
Targets for gene therapy of restenosis
NOS gene therapy for restenosis
HSV-1 gene therapy to prevent intimal hyperplasia
Nonviral gene therapy to prevent intimal hyperplasia
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
Absorbable DES
Bio-absorbable low-dose DES
Drug-eluting stents coated with polymer surfaces
Endeavour DES
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 in clinical trials
Comparison of DES with competing technologies
DES versus coronary artery bypass graft
DES versus bare metal 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
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 for treatment of restenosis by DES
Future role of DES in management of cardiovascular diseases
Stent cost and marketing strategies
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 prospects 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: 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: Improved methods of systemic drug delivery of cardiovascular drugs
Table 2-4: Targeted delivery of therapeutic substances to the cardiovascular system
Table 2-5: Classification of devices for drug delivery to the cardiovascular system
Table 2-6: Various methods of delivery of therapeutic agents for hypertension
Table 2-7: Marketed controlled/ extended release preparation for hypertension
Table 2-8: Drug delivery in ischemic heart disease
Table 2-9: Strategies for cardioprotection
Table 2-10: Methods of delivery of nitrate therapy in angina pectoris
Table 2-11: 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 2013-2023
Table 6-2: Prevalence of cardiovascular disorders in major markets: Europe 2013-2023
Table 6-3: Prevalence of cardiovascular disorders in major markets: Japan 2013-2023
Table 6-4: Values of cardiovascular DDS in major markets 2013-2023
Table 6-5: Markets for innovative technologies for cardiovascular disorders 2013-2023
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 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

Professor K. K. Jain is a neurologist/neurosurgeon by training and has been working in the biotechnology/biopharmaceuticals industry for several years. He received graduate training in both Europe and USA, has held academic positions in several countries and is a Fellow of the Faculty of Pharmaceutical Medicine of the Royal Colleges of UK. Currently he is a consultant at Jain PharmaBiotech. Prof. Jain is the author of 415 publications including 16 books (2 as editor) and 48 special reports, which have covered important areas in biotechnology, gene therapy and biopharmaceuticals.

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