Nanoparticles administered intrapericardially enhance payload myocardial distribution and retention

Victor Segura-Ibarra, Francisca E. Cara, Suhong Wu, David A. Iruegas-Nunez, Sufen Wang, Mauro Ferrari, Arturas Ziemys, Miguel Valderrabano, Elvin Blanco

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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 ~ 2.5 days 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 ~ 7 days. 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.

Original languageEnglish (US)
Pages (from-to)18-27
Number of pages10
JournalJournal of Controlled Release
Volume262
DOIs
StatePublished - Sep 28 2017

Keywords

  • Cardiovascular disease
  • Local drug delivery
  • Nanoparticles
  • Pericardial drug delivery
  • Poly(lactic-co-glycolic acid)

ASJC Scopus subject areas

  • Pharmaceutical Science

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