Preparation and Neuroprotective Effects of Bergamot Essential Oil Liposomes in a PC12 Cell Model of Alzheimer’s Disease

Abstract Bergamot essential oil (BEO) exhibits anxiolytic and antidepressant properties but its biomedical use is restricted by poor solubility, volatility, and instability. Liposomal encapsulation offers a strategy to enhance the stability and bioavailability of volatile plant-derived compounds. In this study, BEO-loaded liposomes were prepared with varying cholesterol-to-lecithin ratios and evaluated for their physicochemical properties and neuroprotective effects in a PC12 cell model of Alzheimer’s disease (AD) induced by amyloid-β fragment Aβ25–35. Liposomes formulated at cholesterol-to-lecithin ratios of 1:4 and 1:5 demonstrated optimal characteristics, with mean particle sizes below 170 nm, narrow size distribution (PDI < 0.2), high surface charge (zeta potential > 30 mV), and encapsulation efficiencies of 70–90%. Cytotoxicity assays confirmed that 20 µM Aβ25–35 reduced PC12 cell viability by 56.41%, increased apoptosis, and induced G0/G1 cell cycle arrest. Pretreatment with BEO liposomes (0.03 mg/mL) significantly improved cell viability, alleviated apoptosis, and mitigated cycle arrest. These findings suggest that liposomal delivery enhances the stability and bioactivity of BEO, enabling protection against Aβ-induced neurotoxicity. The study provides experimental evidence supporting BEO liposomes as a promising neuroprotective formulation for AD intervention.