Abstract 20028: Targeted Nanoparticles Serve as Effective Drug Delivery Vehicles for Cardiovascular-Based Therapy
Introduction: Coronary artery revascularization can lead to ischemia-reperfusion injury (I/R). Pharmacological strategies to prevent I/R are limited by poor retention in circulation and low specificity, which may contribute to systemic side effects. In this study, we generated and characterized biocompatible nanoparticles fabricated from poly(lactic-co-glycolic acid) (PLGA) polymers as a potential therapeutic modality for ischemic heart disease. We aimed to target cells of interest by conjugating the nanoparticle surface with tissue-specific antibodies. We tested the encapsulation of proteins and DNA plasmids for targeted delivery and biological activity.
Methods: A double emulsion-solvent evaporation technique was used to fabricate PLGA nanoparticles. For biodistribution studies, 4-hydroxytamoxifen (OH-tam) were loaded and delivered to transgenic mice harboring an inducible Cre and a fluorescent protein reporter. To target endothelial cells, anti-CD31 antibodies were conjugated to the nanoparticle surface via carbodiimide crosslinkers. Characterization of nanoparticle size and shape, biodistribution, targeting efficiency, and ability to deliver payload were investigated.
Results: Nanoparticles showed consistency of size, spherical shape, and stability in circulation. OH-tam loaded nanoparticles were effective in inducing Cre-recombination. Nanoparticle accumulation within cells was dose-dependent and biodistribution studies revealed majority of uptake in the liver and spleen, with little to no accumulation in the heart, lung, and kidney. Conjugating anti-CD31 antibody increased nanoparticle uptake within endothelial cells, as observed across various organs. In vitro and in vivo studies confirmed ability for targeted delivery of FITC-albumin as well as DNA plasmids that expresses an enhanced GFP.
Conclusions: PLGA nanoparticles provide a robust platform for drug delivery. Conjugating antibodies onto the nanoparticle surface provides a novel and versatile approach to directly target cells of interest, allowing for tissue-specific delivery of bioactive molecules. In particular, PLGA nanoparticles can be used to deliver proteins and DNA plasmids both in vitro and in vivo.
Author Disclosures: N. Nguyen: None. C. Chen: None. Y. Zhang: None. P. Zhao: None. R. Qiao: None. K. Sereti: None. B. Wu: None. R. Ardehali: None.
- © 2016 by American Heart Association, Inc.