Acute Administration of Chitosan Nanoparticles Increases Ca²⁺ 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.

Some Peculiarities in the Dose Dependence of Separate and Combined In Vitro Cardiotoxicity Effects Induced by CdS and PbS Nanoparticles With Special Attention to Hormesis Manifestations

“…12 There are few published studies demonstrating effects of any NPs on cardiomyocytes. In addition to cytotoxicity, reduced contraction amplitudes (with TiO 2 -NPs 13 ), enhanced beating properties (with mesoporous SiO 2 -NPs 14 ), interference with ion channels (with Pt-NPs 15 ), and increased Ca 2þ spikes and local Ca 2þ flux (chitosan NPs 16 ) have been reported. The 2016 overview devoted specially to NPs that cardiotoxicity considers such NP species as zinc, titanium, silver, carbon, silica, and iron oxide but does not mention lead or cadmium in any chemical form.…”

Development of Functional Fluorescent Molecular Probes for the Detection of Biological Substances

“…developed a new group of fluorescent indicators with visible excitation and emission wavelengths to measure free cytosolic Ca 2+ [ 23 ]. Among this group, Fluo-3 and Fluo-4 ( Figure 3 ), have gained widespread acceptance as useful general cytosolic Ca 2+ probes because of their high Ca 2+ affinity, large dynamic range upon Ca 2+ binding, good cell loading properties, and excellent match of the excitation wavelength with the widely used argon ion laser [ 24 , 25 ]. These fluorescent indicators combine the 8-coordinate tetracarboxylate chelating site of 1,2,-bis(Z-aminophenoxyethane- N,N,N',N'-tetraacetic acid with a xanthene chromophore to produce a fluorescein-like fluorophore.…”