Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione

Lyso-7 is a novel synthetic thiazolidinedione, which receptor (pan) agonist of PPAR ?,?/?,? with anti-inflammatory activity. We investigated the cardiotoxicity free in vitro (4.5–450 nM), and loaded polylactic acid nanocapsules (NC) vivo (Lyso-7-NC, 1.6 mg/kg). In previous work, we characterized Lyso-7-NC. administered intravenously Lyso-7, Lyso-7-NC, control, blank-NC once day for seven days mice. assessed cell contraction intracellular Ca2+ transients on single mice cardiomyocytes enzymatically isolated. reduced accelerated relaxation while lowering diastolic reducing transient amplitude. also promoted abnormal ectopic events, isoproterenol dramatically enhanced. Incorporation NC attenuated drug effects prevented its impact relaxation, Ca2+, amplitude, decay kinetics, promotion events. Acute at high concentrations (450 nM) were globally similar to those observed after repeated administration vivo. conclusion, show evidence off-target seen during acute exposure treatment Nano-encapsulation polymeric unwanted effects, particularly events known support life-threatening arrhythmias favored by stress or exercise.