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Nanoformulations reduce cardiotoxicity of doxorubicin – in vivo animal study

Doxorubicin (DOX) is an effective chemotherapeutic agent prescribed for treatment of various neoplasms. Its major disadvantage and side effect is irreversible cardiomyopathy. This study aimed to investigate if a novel nanoformulation can reduce DOX cardiotoxicity under in vivo settings. Biomarkers for cardiotoxicity were serum levels of cardiac troponin T (cTnT) and N-terminal prohormone of brain natriuretic peptide (NT- proBNP), routinely used in the diagnosis of myocardial damage and heart failure. Three different DOX formulations were tested: commercially and clinically approved conventional (DOX) and nanoliposomal DOX formulations (nanoDOX) that were compared with novel nanoformulation based on poly(lactic-co-glycolic acid) (PLGA- DOX).Doxorubicin (DOX) is an effective chemotherapeutic agent prescribed for treatment of various neoplasms. Its major disadvantage and side effect is irreversible cardiomyopathy. This study aimed to investigate if a novel nanoformulation can reduce DOX cardiotoxicity under in vivo settings. Biomarkers for cardiotoxicity were serum levels of cardiac troponin T (cTnT) and N- terminal prohormone of brain natriuretic peptide (NT-proBNP), routinely used in the diagnosis of myocardial damage and heart failure. Three different DOX formulations were tested: commercially and clinically approved conventional (DOX) and nanoliposomal DOX formulations (nanoDOX) that were compared with novel nanoformulation based on poly(lactic-co-glycolic acid) (PLGA- DOX).Tested compounds were administrated by intraperitoneal application to male and female Wistar rats four times, once per week. At the end of experiment, cTnT and NT-proBNP were determined in rat serum samples using the enzyme-linked immunosorbent (ELISA) assay. Significant increase in the TnT concentration was observed in animals treated with DOX, while significant decrease in NT-proBNP concentration was noticed in animals treated with nanoDOX. In males treated with DOX, cTnT was significantly upregulated compared to control animals, while nanoDOX and PLGA-DOX showed no significant effect. Concentration of NT-proBNP decreased in male animals treated with all three types of DOX formulations, while the decrease in concentration was observed in female rats treated with nanoDOX formulation. Obtained results indicate beneficial characteristics of novel nanoformulation towards safer clinical use of antitumor agents and highlight the importance of nanotechnology for cancer medicine.

nanoformulation, doxorubicine, cardiotoxicity

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