Back to Search
Start Over
Nanoparticles administered intrapericardially enhance payload myocardial distribution and retention.
- Source :
-
Journal of Controlled Release . Sep2017, Vol. 262, p18-27. 10p. - Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01683659
- Volume :
- 262
- Database :
- Academic Search Index
- Journal :
- Journal of Controlled Release
- Publication Type :
- Academic Journal
- Accession number :
- 125175692
- Full Text :
- https://doi.org/10.1016/j.jconrel.2017.07.012