In vivo and in silico approaches for evaluating nerolidol-β-cyclodextrin nanoparticles: Antioxidant potential and hormonal modulation in DMBA-induced mammary carcinoma.

The aim of this study is to investigate the chemopreventive effects of nerolidol-β-cyclodextrin nanoparticles (NER-βCD-NPs) on DMBA-induced oxidative stress, lipid, and hormonal disturbances in rats and to characterize their physicochemical properties and molecular interactions with breast cancer targets. NER-βCD-NPs were prepared and HR-TEM and SAED were used for NPs characterization. A total of 36 rats were divided into six groups. Group I served as the control. Group II received a single dose of DMBA (25 mg/rat). Groups III-V were DMBA-injected and treated with NER-βCD-NPs (5, 10, and 20 mg/kg). Group VI received only NER-βCD-NPs (20 mg/kg). After 16 weeks, rats were sacrificed for biochemical and hormonal analysis. Molecular docking of nerolidol was performed with breast cancer targets (ER, PR, and HER2). HR-TEM analysis showed well-defined, near-spherical NER-βCD-NPs with an average size of 27.6 nm. SAED patterns confirmed their polycrystalline structure. DMBA-alone rats exhibited significant decreases in antioxidant activity and increases in lipid peroxidation, lipid profile markers (TC, TG, FFA, and PL), and hormonal levels (ER, PR, and HER2). Treatment with NER-βCD-NPs dose dependently restored antioxidant status, reduced lipid peroxidation and lipid profile disturbances, and normalized hormonal markers. Molecular docking revealed nerolidol exhibited favorable binding to ER (- 7.2 kcal/mol), PR (- 6.6 kcal/mol), and HER2 (- 7.6 kcal/mol), comparable to standard hormonal drugs, with hydrophobic interactions and hydrogen bonds. NER-βCD-NPs significantly ameliorate DMBA-induced oxidative stress, lipid dysregulation, and hormonal imbalance in rats, supported by strong molecular interactions with key breast cancer targets. These findings suggest the potential of NER-βCD-NPs as a promising, safe, and effective chemopreventive agent.