Issue 19, 2024

Novel PLGA-based nanoformulation decreases doxorubicin-induced cardiotoxicity

Abstract

Nanotechnology has the potential to provide formulations of antitumor agents with increased selectivity towards cancer tissue thereby decreasing systemic toxicity. This in vivo study evaluated the potential of novel nanoformulation based on poly(lactic-co-glycolic acid) (PLGA) to reduce the cardiotoxic potential of doxorubicin (DOX). In vivo toxicity of PLGADOX was compared with clinically approved non-PEGylated, liposomal nanoformulation of DOX (LipoDOX) and conventional DOX form (ConvDOX). The study was performed using Wistar Han rats of both sexes that were treated intravenously for 28 days with 5 doses of tested substances at intervals of 5 days. Histopathological analyses of heart tissues showed the presence of myofiber necrosis, degeneration processes, myocytolysis, and hemorrhage after treatment with ConvDOX, whereas only myofiber degeneration and hemorrhage were present after the treatment with nanoformulations. All DOX formulations caused an increase in the troponin T with the greatest increase caused by convDOX. qPCR analyses revealed an increase in the expression of inflammatory markers IL-6 and IL-8 after ConvDOX and an increase in IL-8 expression after lipoDOX treatments. The mass spectra imaging (MSI) of heart tissue indicates numerous metabolic and lipidomic changes caused by ConvDOX, while less severe cardiac damages were found after treatment with nanoformulations. In the case of LipoDOX, autophagy and apoptosis were still detectable, whereas PLGADOX induced only detectable mitochondrial toxicity. Cardiotoxic effects were frequently sex-related with the greater risk of cardiotoxicity observed mostly in male rats.

Graphical abstract: Novel PLGA-based nanoformulation decreases doxorubicin-induced cardiotoxicity

Supplementary files

Article information

Article type
Paper
Submitted
08 12 2023
Accepted
16 4 2024
First published
18 4 2024

Nanoscale, 2024,16, 9412-9425

Novel PLGA-based nanoformulation decreases doxorubicin-induced cardiotoxicity

N. Drinković, M. Beus, R. Barbir, Ž. Debeljak, B. Tariba Lovaković, N. Kalčec, M. Ćurlin, A. Bekavac, D. Gorup, I. Mamić, D. Mandić, V. Micek, P. Turčić, N. Günday-Türeli, E. Türeli and I. Vinković Vrček, Nanoscale, 2024, 16, 9412 DOI: 10.1039/D3NR06269D

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