Novel PLGA-based nanoformulation decreases doxorubicin-induced cardiotoxicity

Area of Science:

• Nanomedicine
• Drug Delivery Systems
• Cardiotoxicity Research

Background:

• Doxorubicin (DOX) is a potent chemotherapy agent with dose-limiting cardiotoxicity.
• Nanotechnology offers potential for targeted drug delivery, reducing systemic side effects.
• Developing safer DOX formulations is crucial for improving cancer patient outcomes.

Purpose of the Study:

• To evaluate the cardiotoxic potential of a novel poly(lactic-co-glycolic acid) (PLGA) nanoformulation of DOX (PLGA-DOX).
• To compare the in vivo cardiotoxicity of PLGA-DOX with conventional DOX (ConvDOX) and liposomal DOX (LipoDOX).

Main Methods:

• Wistar Han rats received intravenous treatments over 28 days.
• Histopathological analysis of heart tissues assessed cardiac damage.
• Biochemical markers (Troponin T) and gene expression (IL-6, IL-8) were analyzed.
• Mass spectra imaging (MSI) evaluated metabolic and lipidomic changes.

Main Results:

• ConvDOX induced severe cardiotoxicity, including necrosis and myocytolysis.
• PLGA-DOX and LipoDOX showed reduced cardiac damage, primarily myofiber degeneration and hemorrhage.
• All formulations increased Troponin T; ConvDOX showed the highest elevation.
• PLGA-DOX demonstrated less inflammatory response and metabolic disruption than LipoDOX and ConvDOX.
• PLGA-DOX induced only mitochondrial toxicity, while LipoDOX showed detectable autophagy and apoptosis.
• Cardiotoxicity was sex-related, with higher risk observed in male rats.

Conclusions:

• PLGA-DOX nanoformulation significantly mitigates doxorubicin-induced cardiotoxicity compared to conventional and liposomal formulations.
• PLGA-DOX exhibits a favorable safety profile with reduced cardiac damage, inflammation, and metabolic disturbances.
• This novel nanoformulation holds promise for safer chemotherapy delivery, particularly in male patients.