Intrapericardial therapy and diagnosis

Spodick, David H.

doi:10.1007/s11886-002-0122-5

Cited by 9 publications

(1 citation statement)

References 24 publications

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“…Higher local drug concentrations can be obtained in the heart, owing principally to lower clearance rates [7, 11]. Consequently, lower doses are required for therapeutic effect, resulting in less systemic exposure of drug, which in turn reduces off-target toxicities [12]. Pericardial delivery has been used to administer a variety of drugs for the treatment of disease, including paclitaxel for inhibition of vascular smooth muscle cell proliferation in restenosis [13], procainamide and digitalis for antiarrhythmic therapy [14], and insulin-like growth factor I for treatment of chronic heart failure [15].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles administered intrapericardially enhance payload myocardial distribution and retention

Segura‐Ibarra

Cara

et al. 2017

Journal of Controlled Release

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Pharmacological therapies for cardiovascular diseases are limited by short-term pharmacokinetics and extra-cardiac adverse effects. Improving delivery selectivity specifically to the heart, wherein therapeutic drug levels can be maintained over time, is highly desirable. Nanoparticle (NP)-based pericardial drug delivery could provide a strategy to concentrate therapeutics within a unique, cardiac-restricted compartment to allow sustained drug penetration into the myocardium. Our objective was to explore the kinetics of myocardial penetration and retention after pericardial NP drug delivery. Fluorescently-tagged poly(lactic-co-glycolic acid) (PLGA) NPs were loaded with BODIPY, a fluorophore, and percutaneously administered into the pericardium via subxiphoid puncture in rabbits. At distinct timepoints hearts were examined for presence of NPs and BODIPY. PLGA NPs were found non-uniformly distributed on the epicardium following pericardial administration, displaying a half-life of ~2.5days in the heart. While NPs were mostly confined to epicardial layers, BODIPY was capable of penetrating into the myocardium, resulting in a transmural gradient. The distinct architecture and physiology of the different regions of the heart influenced BODIPY distribution, with fluorophore penetrating more readily into atria than ventricles. BODIPY proved to have a long-term presence within the heart, with a half-life of ~7days. Our findings demonstrate the potential of utilizing the pericardial space as a sustained drug-eluting reservoir through the application of nanoparticle-based drug delivery, opening several exciting avenues for selective and prolonged cardiac therapeutics.

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