Evaluation of the Cytotoxic Activity of Nanostructured Lipid Carrier Systems for Fatty Acid Amides and Silk Fibroins in Breast Cancer Cell Lines

Breast cancer, a highly prevalent malignancy among women, continues to pose a significant global health challenge, as conventional therapies are often limited by adverse effects. This study developed and evaluated nanostructured lipid carriers (NLCs) encapsulating fatty acid amides (FAAs) semi-synthesized from andiroba oil and combined with silk fibroin (SF) as a novel therapeutic strategy. Methods: FAAs were synthesized via direct amidation and characterized by GC-MS, FT-IR, and ¹³C NMR. These fatty acid amides were then incorporated into NLCs containing SF. The formulation was evaluated for its physicochemical stability, cell selectivity, and cytotoxicity against 4T1 murine breast cancer cells and healthy human fibroblasts. Results: The NLC-FAA/SF formulation exhibited physicochemical stability (average particle size: 136.9 ± 23.6 nm; zeta potential: -8.3 ± 12.0 mV; polydispersity index: 0.19 ± 0.04), indicating a monodisperse and stable system. In vitro cytotoxicity assays demonstrated high selective activity against 4T1 murine breast cancer cells (IC₅₀ = 0.18 ± 0.06 μg/mL) and negligible toxicity to healthy human fibroblasts. Molecular docking studies revealed favorable interactions between the FAAs and cannabinoid receptors CB1 and CB2, with unsaturated FAAs showing higher binding scores and stability, suggesting their potential as cannabinoid receptor ligands. These findings highlight NLC-FAA/SF as a promising, selective, and effective nanoplatform for breast cancer treatment, warranting further investigation into its mechanism of action and in vivo efficacy.