Design of novel nanoformulation to decrease cardiotoxicity of doxorubicin

Doxorubicin (DOX) is a chemotherapeutic agent successfully used for the treatment of various neoplasms, however its use entails risks of side- effects such as irreversible cardiomyopathy [1]. To enhance its pharmaceutic potential, novel nanoformulated poly(lactic-co-glycolic acid) DOX (PLGA) was prepared and their cardiotoxic effects were compared with commercially and clinically approved conventional (CNV) and liposomal (LPS) formulations. Formulations were administrated intraperitoneally to male and female Wistar rats four times, once per week. Then, serum levels of cardiac troponin T (cTnT) and N-terminal prohormone of brain natriuretic peptide (NT- proBNP) were quantified with ELISA assays, and expression of inflammation-related genes (IL-6, IL-8, TNFα and IL-1β) in heart tissue of treated and control rats was evaluated using Real-Time PCR. Heart cryosections of treated and control rats were analyzed by imaging mass spectrometry (IMS). CNV and LPS formulations significantly increased cTNT levels compared to control animals, while PLGA showed no such effect. NT-proBNP was decreased in animals treated with CNV and LPS, while no changes were observed for treatment with PLGA formulation. CNV significantly increased expression of IL-6 and IL-8 in heart tissue, which was not observed in PLGA-treated rats. Results of IMS analysis have shown reduced expression of inflammation markers in PLGA-treated rats compared to CNV- and LPS-treated animals. Therefore, novel PLGA formulation demonstrated lower inflammatory potential compared to clinically approved CNV and LPS, indicating the potential for novel nanoformulations for safer drug delivery in cancer therapy.