Delivery of drugs, growth factors, genes and stem cells via intrapericardial, epicardial and intramyocardial routes for sustained local targeted therapy of myocardial disease

ABSTRACT

Introduction: Local myocardial delivery (LMD) of therapeutic agents is a promising strategy that aims to treat various myocardial pathologies. It is designed to deliver agents directly to the myocardium and minimize their extracardiac concentrations and side effects. LMD aims to enhance outcomes of existing therapies by broadening their therapeutic window and to utilize new agents that could not be otherwise be implemented systemically.

Areas covered: This article provides a historical overview of six decades LMD evolution in terms of the approaches, including intrapericardial, epicardial, and intramyocardial delivery, and the wide array of classes of agents used to treat myocardial pathologies. We examines delivery of pharmaceutical compounds, targeted gene transfection and cell implantation techniques to produce therapeutic effects locally. We outline therapeutic indications, successes and failures as well as technical approaches for LMD.

Expert opinion: While LMD is more complicated than conventional oral or intravenous administration, given recent advances in interventional cardiology, it is safe and may provide better therapeutic outcomes. LMD is complex as many factors impact pharmacokinetics and biologic result. The choice between routes of LMD is largely driven not only by the myocardial pathology but also by the nature and physicochemical properties of the therapeutic agents.

KEYWORDS:

• Epicardial drug delivery
• intramyocardial drug delivery
• intrapericardial drug delivery
• heart disease
• therapy

Article highlights

• Local myocardial delivery (LMD) of drugs, growth factors, genes and cells aims to administer therapeutic agents directly to the myocardium and minimize their extracardiac concentrations and side effects.

• Over six decades, LMD has progressed from basic open chest experiments in small animals studying myocardial drug distribution to Phase III clinical trials of heart failure therapy using minimally invasive delivery of stem cells.

• LMD utilizes three routes: intrapericardial, epicardial and intramyocardial approaches, each of them having advantages over the other, in terms of volume of delivery, clearance, depth of distribution, and precision of the targeting.

• LMD has been utilized to treat myocardial pathologies by administering antiarrhythmic, anti-inflammatory, inotropic and angiogenesic agents.

• Of all therapeutic agents, LMD of stem cells has been most successful to treat myocardial pathology and has been undergoing multiple clinical studies.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.