The aim of this study was to investigate the potential of natural melanin nanoparticles (MNPs) as carriers for oxaliplatin (OXP) delivery, with glycol chitosan (GC) surface modification to improve dispersion behavior and drug interaction. The isolated MNPs were spherical with an average diameter of 148 ± 28 nm, which increased to 261 ± 39 nm after GC coating. The particle size decreased to 148 ± 59 nm after OXP loading. Physicochemical characterization confirmed surface modification and drug association. The OXP-loaded GC-MNP formulation showed a loading efficiency of 67.8 ± 4.6% and a biphasic release profile, with an initial rapid release followed by complete drug release within 24 h. Release kinetic analysis showed the best fit with the first-order model, indicating concentration-dependent release behavior. Biological studies demonstrated time-dependent responses in MCF-7 cells. All tested formulations showed low cytotoxicity at 6 h. However, OXP-loaded GC-MNP exhibited higher cytotoxicity than free OXP under selected conditions. Furthermore, concentration-dependent genotoxic effects were observed in comet assay experiments. These findings suggest that GC-coated melanin nanoparticles may serve as a promising carrier platform for short-term modulation of OXP delivery in breast cancer applications.
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