Development of ascorbyl palmitate based hydrophobic gold nanoparticles as a nanocarrier system for gemcitabine delivery

Breast cancer remains a major global health challenge, commonly treated with gemcitabine hydrochloride (GEM). However, GEM's short half-life and rapid metabolism limit its therapeutic efficacy. This study introduces a novel nano-drug delivery system based on gold nanoparticles (AuNPs) modified with ascorbyl palmitate (AsP) to improve GEM stability and performance. AuNPs were surface-modified via single-phase emulsification to form a hydrophobic AsP-coated nanoemulsion. Two formulations were prepared: Au-GEM-AsP-MOD (128.5 nm, - 18.3 mV, 89.5% encapsulation efficiency) and Au-GEM-AsP-Phys (106 nm, - 15.9 mV, 87% encapsulation efficiency). The Au-GEM-AsP-MOD system exhibited superior hydrophobicity, controlled GEM release (93% over 72 h), and enhanced cytotoxicity (IC₅₀ = 0.44 µg/mL) in 4T1 breast cancer cells compared with free GEM and physically adsorbed formulations. Furthermore, it maintained stability for six months under stress conditions (25 ± 2 °C, 60 ± 5% RH), indicating robustness and extended shelf life due to effective surface modification. The study highlights the synergistic effects of AsP in enhancing the therapeutic efficacy of Au-GEM-based formulations, supporting its role as a key component in combination therapy. This research lays the foundation for future development of hydrophobic nanomedical devices combining GEM and AsP for therapeutic and diagnostic applications in nanomedicine.