Objective To develop formulation-optimized ganoderic acid A liposomes (GA-Lips) with improved stability and high encapsulation efficiency, and to evaluate their cellular uptake efficiency and in vitro antitumor activity. Methods GA-Lips were prepared using the thin-film hydration method, and formulation parameters were optimized by varying the ratios of GAA, phospholipids, and cholesterol. Particle size, ζ potential, and morphology were characterized. In vitro drug release and formulation stability were evaluated under different media, dilution, and storage conditions. Hemocompatibility was assessed by hemolysis assays. Cellular uptake efficiency was examined using confocal laser scanning microscopy and flow cytometry. Antiproliferative effects and apoptosis induction in HepG2 cells were analyzed using CCK-8 and Annexin V-FITC/PI assays, respectively. Results The optimized GA-Lips exhibited a uniform spherical morphology with a mean particle size of (74.52 ± 1.00) nm, a PDI of 0.26 ± 0.01, and a ζ potential of (-46.75 ± 1.61) mV. The formulation showed sustained drug release, excellent stability under various test conditions, and negligible hemolytic activity. GA-Lips significantly enhanced cellular uptake efficiency in HepG2 cells compared with free GAA. Moreover, GA-Lips exhibited pronounced cytotoxic effects and markedly increased apoptosis induction. Conclusion The optimized GA-Lips demonstrated favorable stability and hemocompatibility, effectively enhancing the cellular uptake efficiency and in vitro antitumor efficacy of GAA. These results support the potential of GA-Lips as a promising nanocarrier system for ganoderic acid A and provide a foundation for further in vivo and mechanistic studies.

ganoderic acid A  /  liposomes  /  thin-film dispersion  /  formulation optimization  /  antitumor activity  /  nanocarrier system