Cardiovascular Drug Delivery - technologies, markets and companies |
|
|
0. Executive Summary ......... 10 1. Cardiovascular Diseases .. 12 Introduction.. 12 History of cardiovascular drug delivery........ 12 Overview of cardiovascular disease ............. 13 Coronary artery disease ........13 Angina pectoris ...............13 Limitations of current therapies for myocardial ischemic disease ................13 Cardiomyopathies ................13 Cardiac arrhythmias .............14 Congestive heart failure ........14 Peripheral arterial disease .....14 Current management.......15 Atherosclerosis ....................15 The endothelium as a target for cardiovascular therapeutics....15 Molecular cardiology ............. 16 Cardiogenomics ...................16 Cardioproteomics .................16 Personalized cardiology ........ 17 Pharmacogenomics of cardiovascular disorders ......................17 Modifying the genetic risk for myocardial infarction ................18 Management of heart failure..18 Management of hypertension.19 Pharmacogenomics of diuretic drugs.........19 Pharmacogenomics of ACE inhibitors ........19 Management of hypertension by personalized approach .....20 Pharmacogenetics of lipid-lowering therapies..20 Polymorphisms in genes involved in cholesterol metabolism ......................20 Role of eNOS gene polymorphisms ...........21 Important advances in cardiovascular therapeutics............ 21 Drug delivery, biotechnology and the cardiovascular system..................... 22 2. Methods for Drug Delivery to the Cardiovascular System ..................... 24 Introduction.. 24 Routes of drug delivery to the cardiovascular system......... 24 Local administration of drugs to the cardiovascular system 24 Intramyocardial drug delivery 24 Drug delivery via coronary venous system .....25 Intrapericardial drug delivery.25 Formulations for drug delivery to the cardiovascular system..................... 25 Sustained and controlled release...................26 Programming the release at a defined time ......................26 Dosage formulation of calcium channel blockers................27 Sustained and controlled release verapamil ......................27 Methods of administration of proteins and peptides ................27 Delivery of peptides by subcutaneous injection .................28 Depot formulations and implants..............28 Poly(ethylene glycol) technology ..............28 Microencapsulation for protein delivery .....29 Localized delivery of biomaterials for tissue engineering.....29 Oral delivery of proteins and peptides .......29 DDS to improve systemic delivery of cardiovascular drugs . 30 Nanotechnology-based drug delivery .............31 Targeted drug delivery to the cardiovascular system.......... 32 Immunotargeting of liposomes to activated vascular endothelial cells ..............33 PEGylated biodegradable particles targeted to inflamed endothelium ...............33 Devices for cardiovascular drug delivery...... 34 Local drug delivery by catheters....................34 Microneedle for periarterial injection ..............35 Nanotechnology-based devices for the cardiovascular system ..36 Liposomal nanodevices for targeted cardiovascular drug delivery ...............36 Nanotechnology approach to the problem of “vulnerable plaque”................37 Role of cardiovascular imaging in cardiovascular therapeutics..37 Chronopharmacotherapy of cardiovascular diseases........... 38 Drug delivery in the management of cardiovascular disease...................... 38 Drug delivery in the management of hypertension..................38 - 4 - Transnasal drug delivery for hypertension .39 Transdermal drug delivery for hypertension......................39 Oral extended and controlled release preparations for hypertension ...........40 Long-acting hypertensives for 24 h blood pressure control .40 Drug delivery to control early morning blood pressure peak41 Role of drug delivery in improving compliance with antihypertensive therapy......................41 Drug delivery for congestive heart failure .......42 Oral human brain-type natriuretic peptide .42 Nitric oxide-based therapies for congestive heart failure.....42 Automated drug delivery system for cardiac failure ...........42 DDS in the management of ischemic heart disease.................42 Intravenous emulsified formulations of halogenated anesthetics.................43 Injectable peptide nanofibers for myocardial ischemia .......44 Delivery of angiogenesis-inducing agents for myocardial ischemia..............44 Drug delivery in the treatment of angina pectoris...................44 Sustained and controlled-release nitrate for angina pectoris ......................45 Transdermal nitrate therapy ....................45 Controlled release calcium blockers for angina pectoris ......46 Drug delivery in the management of pulmonary hypertension..46 Anticoagulation in cardiovascular disease .......47 Oral heparin ...................47 Low molecular weight heparin-loaded polymeric nanoparticles ...................47 Transdermal anticoagulants.....................48 Thrombolysis for cardiovascular disorders ......48 Use of ultrasound to facilitate thrombolysis ......................48 Delivery of alteplase through the AngioJet rheolytic catheter .....................49 Drug delivery for peripheral arterial disease ...49 Delivery of thrombolytic agent to the clot through a catheter.....................49 Immune modulation therapy for PAD ........50 NO-based therapies for peripheral arterial disease.............50 Drug delivery in the management of hypercholesterolemia......50 Controlled/sustained release formulations of statins ..........50 Combinations of statins with other drugs to increase efficacy.....................51 Controlled release fenofibrate ..................52 Extended release nicotinic acid ................52 Intravenous infusion of lipoprotein preparations to raise HDL.....................53 Innovative approaches to hypercholesterolemia ................53 Single dose therapy for more than one cardiovascular disorder 54 3. Cell Therapy for Cardiovascular Disorders ..................... 56 Introduction.. 56 Inducing the proliferation of cardiomyocytes...56 Role of stem cells in repair of the heart..........56 Cell therapy for atherosclerotic coronary artery disease ..........56 Transplantation of myoblasts for myocardial infarction............57 MyoCell™ (Bioheart)........57 Cellular cardiomyoplasty ..58 Intracoronary infusion of bone marrow-derived cells for AMI ...58 Cord blood stem cells for myocardial infarction ......................58 Transplantation of stem cells for myocardial infarction ............59 Transplantation of embryonic stem cells....59 Transplantation of hematopoietic stem cells......................59 Intracoronary infusion of mobilized peripheral blood stem cells ..................59 Human mesenchymal stem cells for cardiac regeneration ...60 Cytokine preconditioning of human fetal liver CD133+ SCs.60 Transplantation of expanded adult SCs derived from the heart...................61 Transplantation of endothelial cells...........61 Transplantation of genetically modified cells ...61 Transplantation of cells secreting vascular endothelial growth factor...........61 Transplantation of genetically modified bone marrow stem cells.................62 Cell transplantation for congestive heart failure......................62 Myoblasts for treatment of congestive heart failure ...........62 Injection of adult stem cells for congestive heart failure.....62 Role of cell therapy in cardiac arrhythmias .....63 Atrioventricular conduction block..............63 Ventricular tachycardia ....64 ESCs for correction of congenital heart defects..................64 Cardiac progenitors cells for treatment of heart disease in children..................64 Stem cell therapy for peripheral arterial disease.....................65 Clinical trials of cell therapy in cardiovascular disease.............65 A critical evaluation of cell therapy for heart disease...............66 - 5 - 4. Gene Therapy for Cardiovascular Disorders ................... 68 Introduction.. 68 Techniques of gene transfer to the cardiovascular system.. 69 Direct plasmid injection into the myocardium..69 Catheter-based systems for vector delivery ....69 Ultrasound microbubbles for cardiovascular gene delivery .......70 Vectors for cardiovascular gene therapy.........70 Adenoviral vectors for cardiovascular diseases ..................70 Plasmid DNA-based delivery in cardiovascular disorders.....71 Intravenous rAAV vectors for targeted delivery to the heart ......................71 Hypoxia-regulated gene therapy for myocardial ischemia ........71 Angiogenesis and gene therapy of ischemic disorders .............72 Therapeutic angiogenesis vs. vascular growth factor therapy ...72 Gene painting for delivery of targeted gene therapy to the heart.....................73 Gene delivery to vascular endothelium...........73 Targeted plasmid DNA delivery to the cardiovascular system with nanoparticles ......................73 Gene delivery by vascular stents...................74 Gene therapy for genetic cardiovascular disorders ............. 75 Genetic disorders predisposing to atherosclerosis...................75 Familial hypercholesterolemia75 Apolipoprotein E deficiency....76 Hypertension 77 Genetic factors for myocardial infarction ........77 Acquired cardiovascular diseases ................ 77 Coronary artery disease with angina pectoris..78 Ad5FGF-478 Ischemic heart disease with myocardial infarction ..................78 Myocardial repair with IGF-1 therapy ........79 Congestive heart failure ........80 Rationale of gene therapy in CHF .............80 Genetic manipulation of b-adrenergic receptor system in CHF ....................80Intracoronary adenovirus-mediated gene therapy for CHF ..80 AngioCell gene therapy for congestive heart failure ...........81 nNOS gene transfer in CHF......................81 Gene therapy for cardiac arrhythmias ............81 Gene therapy and heart transplantation .........83 Gene therapy for peripheral arterial disease ...83 Angiogenesis by gene therapy .................83 HIF-1 a gene therapy for peripheral arterial disease ...........83HGF gene therapy for peripheral arterial disease ...............84 Ischemic neuropathy secondary to peripheral arterial disease....................84 Maintaining vascular patency after surgery.....84 Antisense therapy for cardiovascular disorders .................. 85 Antisense therapy for hypertension ...............86 Antisense therapy for hypercholesterolemia....86 RNAi for cardiovascular disorders................ 87 RNAi for hypercholesterolemia ......................87 Future prospects of gene therapy of cardiovascular disorders ................... 88 Companies involved in gene therapy of cardiovascular disorders .............. 88 5. Drug-Eluting Stents ......... 90 Introduction.. 90 Percutaneous transluminal coronary angioplasty ....................90 Stents.........90 Restenosis ..... 90 Pathomechanism..................90 Treatment...91 Nitric oxide-based therapies for restenosis .....91 Carbon monoxide inhalation for preventing restenosis ............92 Antisense approaches for prevention of restenosis after angioplasty ................92 Gene therapy to prevent restenosis after angioplasty .............93 Techniques of gene therapy for restenosis.95 NOS gene therapy for restenosis ..............95 Non-viral gene therapy to prevent intimal hyperplasia .......96 HSV-1 gene therapy to prevent intimal hyperplasia ...........96 Drug delivery devices for restenosis ..............96 Local drug delivery by catheter .....................97 Absorbable metal stents........97 Antiproliferative drugs encapsulated in biodegradable nanoparticles ................97 Drug-eluting stents............... 98 Various types of DES ............98 - 6 - CYPHER® sirolimus-eluting coronary stent 98 Sirolimus-eluting vs paclitaxel-eluting stents ....................99 Paclitaxel-eluting stents ...99 Dexamethasone-eluting stents............... 100 NO-generating stents..... 100 Dexamethasone-eluting stents............... 100 Novel technologies for DES.. 101 Stents for delivery of gene therapy......... 101 Stem cell-based stents... 101 Drug-eluting stents coated with polymer surfaces ........... 102 Absorbable DES ............ 102 Endeavour DES ............. 102 New coating materials for DES ............... 103 Bio-absorbable low-dose DES ................ 104 VAN 10-4 DES .............. 104 Nanotechnology-based stents ..................... 104 Nanocoated DES ........... 104 Nanopores to enhance compatibility of DES .................... 105 The ideal DES .................... 105 Companies developing drug-eluting stents ... 106 Clinical trials of drug-eluting stents ............. 107 Measurements used in clinical trials of DES .................... 107 TAXUS paclitaxel-eluting stents.............. 107 Everolimus-eluting coronary stents......... 108 XIENCE™ V Everolimus-Eluting coronary stent system..... 108 COSTAR II clinical trial... 109 Endeavor RESOLUTE zotarolimus-eluting stent system..... 109 CUSTOM I clinical trial ... 110 Comparison of DES in clinical trials......... 110 Comparison of DES with competing technologies.................. 111 DES versus coronary artery bypass graft. 111 DES versus bare metal stents ................ 111 DES vs BMS for off-label indications ....... 113 Role of DES in cases of bare-metal in-stent restenosis ..... 113 DES versus balloon catheter coated with paclitaxel.......... 114 DES versus intracoronary radiation therapy for recurrent stenosis ............ 114 Cost-effectiveness of DES ... 114 Safety issues of DES........... 115 Adverse reactions to DES ...................... 115 Risk of clotting with DES 115 Clopidogrel use and long-term outcomes of patients receiving DES .......... 117 Effect of blood clot on release of drug from DES.............. 117 Use of magnetized cell lining to prevent clotting of DES ... 118 Long-term safety studies of DES ............ 118 Regulatory issues of DES .... 119 FDA perspective on risk of DES thrombosis... 120 Future prospects for treatment of restenosis by DES ........ 120 Future role of DES in management of cardiovascular diseases ................. 120 Stent cost and marketing strategies ....... 121 Improvements in stent technology ......... 121 Bioabsorbale stent.............. 122 6. Markets for Cardiovascular Drug Delivery.................... |
|