Therapeutic payload delivery to the myocardium: Evolving strategies and obstacles
Tarek Shazly, Arianna Smith, Mark J. Uline, Francis G. Spinale
Abstract
Localized delivery methods aim to achieve therapeutic payload concentrations at specific sites in the body while minimizing off-target delivery/accumulation. An emerging strategy to treat multiple cardiac pathologies is localized payload delivery to the myocardium, which has shown promise to advance treatment options for a wide range of disease states. Candidate payloads for cardiac therapies include pharmacological molecules/drugs, genes, cells, or a combination of these entities, all of which could be administered alone or in conjunction with implantable biomaterials that promote their localization. For example, a recent review highlighted extensive preclinical and clinical studies that support cell-based myocardial repair and regeneration in varied cardiac disease states despite challenges in delivery, with demonstrated reductions in inflammation and fibrosis, promotion of angiogenesis, and in some cases recovery of cardiac function. Irrespective of the specific payload, localized delivery offers better spatiotemporal control of myocardial concentrations compared with traditional oral or systemic intravenous administrations, thereby narrowing the therapeutic window by increasing payload bioavailability. Indeed, the clinical translation of the diverse myocardial payloads with manifest therapeutic potential will largely depend on the effectiveness/adoptability of the employed delivery method.