A novel aminohydroxy sulfonamide formulated in PEGylated liposomes with potential antitumor activity

Caddeo C.

First

;Nigro I.;Chiummiento L.;Funicello M.;Lupattelli P.;Santarsiere A.;Fernandez-Busquets X.;Valenti D.;Rosa E.;Miglionico R.;Armentano M. F.;Vassallo A.

2025-01-01

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Abstract

Cancer ranks as a leading cause of death worldwide, with liver cancer being one of the most commonly diagnosed. Currently, several molecules are being studied in order to find new therapeutic options that can reduce cancer recurrence rate and increase patient survival. This study proposes PEGylated liposomes for the delivery of a newly synthesized aminohydroxy sulfonamide, BupM-NH2, which has shown dose-dependent cytotoxicity towards hepatic tumor cells. The prepared PEG-liposomes were nanosized, spherical, and unilamellar, as shown by light scattering data and cryo-TEM micrographs. The physical stability of the PEG-liposomes was preserved when tested in simulated body fluids. Similar results were found for the storage stability evaluation. Furthermore, the PEG-liposomes efficiently entrapped BupM-NH2 and modulated its release. The antitumor activity of BupM-NH2 in PEG-liposomes was assessed in vitro in hepatocarcinoma cells. The viability assay showed that PEG-liposomes were able to control the release of BupM-NH2 over time and induce the death of HepG2 cells at a concentration about two-times lower than that required by free BupM-NH2 (IC50: 33.31 vs. 57.05 μM). Furthermore, the liposomal formulation showed a less cytotoxic effect against non-cancerous cell line (IHH) compared to the free molecule (IC50 > 200 vs. 106.9 μM), encouraging further investigation to confirm its effective and safe use.