Abstract
Summary
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 2008 to
2018 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
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