Gold nanoparticles and their conjugate with Simdax significantly reduced hydrothorax and demonstrated superior cardioprotective effects compared to Simdax alone in a rat model of heart failure.
Do gold nanoparticles and their conjugate with levosimendan improve heart failure regression in a rat model of doxorubicin-induced heart failure?
Gold nanoparticles and their conjugate with levosimendan demonstrate significant cardioprotective effects and improve heart failure regression in a rat model of doxorubicin-induced heart failure.
p-value: p=<0.01
INTRODUCTION: Nanoscale gold particles (AuNPs) have wide perspectives for biomedical applications because of their unique biological properties, as antioxidative activity and potentials for drug delivery. AIMS AND OBJECTIVES: The aim was to test effects of AuNPs using suggested heart failure rat model to compare with proved medication Simdax, to test gold nanoparticle for drug delivery, and to test sonoporation effect to increase nanoparticles delivery into myocardial cells. MATERIAL AND METHODS: We performed biosafety and biocompatibility tests for AuNPs and conjugate with Simdax. For in vivo tests, we included Wistar rats weighing 180-200 g (n = 54), received doxorubicin in cumulative dose of 12.0 mg/kg to model advance heart failure, registered by ultrasonography. We formed six groups: the first three groups of animals received, respectively, 0.06 ml Simdax, AuNPs, and conjugate (AuNPs-Simdax), intrapleurally, and the second three received them intravenously. The seventh group was control (saline). We performed dynamic assessment of heart failure regression in vivo measuring hydrothorax. Sonoporation of gold nanoparticles to cardiomyocytes was tested. RESULTS: We designed and constructed colloidal, spherical gold nanoparticles, AuNPs-Simdax conjugate, both founded biosafety (in cytotoxicity, genotoxicity, and immunoreactivity). In all animals of the six groups after the third day post-medication injection, no ascites and liver enlargement were registered (P < 0.001 vs controls). Conjugate injection showed significantly higher hydrothorax reduction than Simdax injection only (P < 0.01); gold nanoparticle injection showed significantly higher results than Simdax injection (P < 0.05). AuNPs and conjugate showed no significant difference for rat recovery. Difference in rat life continuity was significant between Simdax vs AuNPs (P < 0.05) and Simdax vs conjugate (P < 0.05). Sonoporation enhances AuNP transfer into the cell and mitochondria that were highly localized, superior to controls (P < 0.01 for both). CONCLUSIONS: Gold nanoparticles of 30 nm and its AuNPs-Simdax conjugate gave positive results in biosafety and biocompatibility in vitro and in vivo. AuNPs-Simdax and AuNPs have similar significant cardioprotective effects in rats with doxorubicin-induced heart failure, higher than that of Simdax. Intrapleural (local) delivery is preferred over intravenous (systemic) delivery according to all tested parameters. Sonoporation is able to enhance gold nanoparticle delivery to myocardial cells in vivo.
Spivak et al. (Mon,) conducted a other in Doxorubicin-induced heart failure (n=54). Gold nanoparticles and AuNPs-Simdax conjugate vs. Simdax alone and saline control was evaluated on Hydrothorax reduction (p=<0.01). Gold nanoparticles and their conjugate with Simdax significantly reduced hydrothorax and demonstrated superior cardioprotective effects compared to Simdax alone in a rat model of heart failure.