Engineered nanostructured lipid carrier encapsulating thymoquinone and resveratrol to prevent Bisphenol S induced cytotoxicity.

Nanostructured lipid carriers (NLCs) are diverse colloidal systems that enhance the solubility, stability, and bioavailability of bioactive compounds. Herein, we developed a co-loaded NLC encapsulating thymoquinone (TQ) and resveratrol (RV) to enhance prevention against globally emerging endocrine disruptor bisphenol S (BPS) induced cytotoxicity in NRK-52E cells. The formulation components were rationally optimised, achieving high encapsulation efficiencies for TQ (99.42% ± 0.08) and RV (98.60% ± 0.12), a particle size of 123.66 ± 6.32 nm, and a polydispersity index of 0.37 ± 0.04, indicating stable, homogeneous, quasi-spherical particles as observed in TEM. Interfacial encapsulation and reduced crystallinity observed by FTIR and XRD analyses, respectively, supported the formation of an imperfect core-shell structure. The drug-release profile indicated a diffusion-dominated, matrix-relaxation-assisted transport mechanism. In vitro assays demonstrated a strong cytoprotective effect of TQRV-NLCs at 0.01 μg/mL, comparable to 1 μg/mL free drugs, indicating a significant improvement in therapeutic efficacy. TQRV-NLCs markedly reduced BPS-induced oxidative stress, mitochondrial depolarisation, loss of cell migration, and loss of membrane integrity, while restoring membrane integrity, normalising cell cycle distribution, and preserving nuclear morphology in NRK-52E cells. In summary, this study provides proof of concept that TQRV-NLCs markedly enhance efficacy, confer superior cytoprotection, and offer preventive effects, presenting a promising strategy for renal protection against BPS.