Mollification of doxorubicin (DOX)-mediated cardiotoxicity using conjugated chitosan nanoparticles with supplementation of propionic acid

• Main Authors: Siva, Durairaj, Abinaya, Subramanian, Rajesh, Durairaj, Archunan, Govindaraju, Padmanabhan, Parasuraman, Gulyás, Balázs, Achiraman, Shanmugam
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Medicine; Doxorubicin; Chitosan Nanoparticles
• Online Access: https://hdl.handle.net/10356/160657
• Institution: Nanyang Technological University

Doxorubicin is an extensively prescribed antineoplastic agent. It is also known for adverse effects, among which cardiotoxicity tops the list. The possible mechanism underlying doxorubicin (DOX)-mediated cardiotoxicity has been investigated in this study. Further, to reduce the DOX-mediated cardiotoxicity, DOX was conjugated with Chitosan Nanoparticles (DCNPs) and supplemented with propionic acid. Initially, the drug loading efficacy and conjugation of DOX with chitosan was confirmed by UV-Visible Spectroscopy (UV) and Fourier Transform Infrared Spectroscopy (FTIR). The average sizes of the synthesized Chitosan Nanoparticles (CNPs) and DCNPs were measured by Dynamic Light Scattering (DLS) analysis as 187.9 ± 1.05 nm and 277.3 ± 8.15 nm, respectively, and the zeta potential values were recorded as 55.2 ± 0.7 mV and 51.9 ± 1.0 mV, respectively. The size and shape of CNPs and DCNPs were recorded using a High-Resolution Electron Microscopy (HRTEM). The particles measured <30 nm and 33-84 nm, respectively. The toxic effects of DCNPs and propionic acid were evaluated in rat model. The data from the electrocardiogram (ECG), cardiac biomarkers, Peroxisome proliferator-activated receptor gamma (PPARγ) and histological observations indicated evidence of DOX-mediated cardiotoxicity, whereas the administration of DCNPs, as well as Propionic Acid (PA), brought about a restoration to normalcy and offered protection in the context of DOX-induced cardiotoxicity.