Acute Administration of Chitosan Nanoparticles Increases Ca<sup>2+</sup> Leak in Rat Cardiomyocytes

Abstract

Polymeric nanoparticles like chitosan nanoparticles may be used to deliver drugs to particular organs, such as heart. However, due to the lack of information about acute effects of chitosan nanoparticles in cardiac calcium handling, we evaluated the same in intact rat left ventricular myocytes. Chitosan nanoparticles were synthesized by ionic gelation method for three different concentrations of chitosan and tripolyphosphate (TPP) such as 1:1, 2:1 and 3:1, respectively. The size of the particles was below 100 nm for the 2:1 and 3:1 chitosan:TPP ratio and 300 nm for 1:1 ratio. The particles synthesized in 3:1 ratio were incubated for 0, 15, 30 and 60 minutes with Fluo-3 loaded cardiomyocytes, their effects were evaluated in local Ca2+ release events using confocal microscopy and compared with control cells. Chitosan nanoparticles increased the amplitude and size of Ca2+ spark by 14.1% and 24.1% at 30 minutes of incubation; while the increment was 24.7% and 28.4% at 60 minutes respectively. Accordingly, rising time of Ca2+ sparks was decreased by 47% at 30 minutes. These changes were reflected in increased local Ca2+ flux by 58.3% and spark-mediated Ca2+ leak by 145.9% and 146.5% at 30, and 60 minutes, respectively. Hence, these results indicate that chitosan nanoparticles modify the properties of local Ca2+ release events mainly at short incubation times and must be taken into account while using these nanoparticles in drug delivery.