Synthesis, structural characterization, and antitumor effect of quercetin-loaded chitosan nanoparticles-stabilized pickering emulsion via suppressing the PI3K/AKT/mTOR signaling pathway

Quercetin, a major polyphenolic flavonoid phytoconstituent, exhibits diverse pharmacological activities, including antiviral, antimicrobial, anticancer, and anti-inflammatory effects, and is used in the treatment of metabolic and allergic disorders. However, its pharmaceutical applications are limited by instability, poor aqueous solubility, low permeability, and reduced oral bioavailability. The primary objective of the present study was to overcome these limitations by enhancing the bioavailability and permeability of quercetin by synthesizing Pickering emulsions (PEs) against hepatocellular carcinoma. PEs were prepared by emulsifying an aqueous nanoparticle phase with an oil phase containing quercetin. Quercetin-loaded (CSNPs-QPE) and unloaded (CSNPs-UPE) Pickering emulsions with average particle sizes of ≤240 nm and monodisperse characteristics were successfully fabricated. The PEs were characterized using UV–Vis spectrophotometry, particle imaging (Cell Imager EVOS FL), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The encapsulation efficiency (EE) of the quercetin-loaded PE was 88.8%. In vitro release kinetics demonstrated a sustained release of quercetin from CSNPs-QPE, particularly at pH 4.0. Cytotoxicity assays revealed significant cancer cell–killing activity of CSNPs-QPE, comparable to the standard drug doxorubicin, in HepG2 liver cancer cells. Furthermore, CSNPs-QPE promoted apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway in liver cancer cells with lower IC 50 (< ∼4.5 µg/mL) values as compared to doxorubicin (> ∼ 4 µg/mL). Taken together, our findings support the potential of quercetin-loaded chitosan Pickering emulsions as controlled drug-delivery carriers for suppressing liver cancer cell growth.