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MASS SPECTROMETRY IMAGING FOR NEPHROTOXICITY EVALUATION OF DIFFERENT DOXORUBICIN FORMULATIONS

The clinical application of the cytotoxic drug, doxorubicin (DOX), is limited by its toxicity to non-cancerous tissues which is likely to induce inflammatory changes in kidney tissues.1 Nanoformulations as novel drug delivery systems may favor site-specific drug accumulation and consequently reduce the harmful effects of DOX on non-targeted tissues.2 This study employed mass spectrometry imaging (MSI) to investigate the effects of different DOX formulations on non-targeted kidney tissues. The biochemical changes in kidney cryosections of Wistar rats treated intraperitoneally during 28 days (once per week) wth liposomal (LPS) and poly(lactic-co-glycolic acid) (PLGA)-based nanoformulations were compared to those induced by the conventional (CNV) formulation. The results showed that there was a significant overlap between different treatments, as demonstrated by principal component analysis (PCA) and Volcano plots of the average mass spectra. However, nanoformulation-specific fingerprint consisting of 59 m/z values was identified for the LPS and PLGA treatments, while histochemical fingerprint of 22 significant m/z values was found for the CNV formulation. The identified m/z values were associated with processes such as apoptosis, cell migration, and proliferation, and were confirmed by a metabolome database search. Further analysis showed that the effects of CNV and PLGA formulations were tissue-nonselective with greater histochemical alterations, while LPS caused the least significant changes in m/z values and showed more specific distribution in the kidney cortex substructures. The study demonstrated the potential of MSI in effectively differentiating the effects of DOX formulations on non-targeted tissues, highlighting its importance in drug development.3

Doxorubicin ; Mass spectrometry ; Nanoformulations

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