Preparation of ginsenoside compound-K mixed micelles with improved retention and antitumor efficacy

INTRODUCTION: Ginsenoside compound K (CK) has effects on cell-cycle regulation, tumor growth inhibition, and apoptosis induction. However, it has limited applications in clinical settings because of its low solubility and poor absorption. METHODS: To overcome these limitations, we aimed to develop a mixed micellar system composed of phosphatidylcholine (PC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol 2000 (DSPE PEG 2000; DP). CK encapsulated in PC/DP mixed micelles had enhanced solubility, permeability, and retention effects. RESULTS: Compared to free CK, the CK PC/DP micellar system exhibited improved anticancer effects in vitro, including cell-cycle arrest, apoptosis, and anti-invasion in human lung carcinoma A549 cells. The significant proapoptotic effect was reflected by increased chromosomal condensation, annexin V/propidium iodide staining, and related protein expression. In vitro cellular uptake and optical mouse imaging in vivo suggested that the improved antitumor effect was caused primarily by enhanced uptake and tumor targeting. Furthermore, an in vivo antitumor efficacy study indicated that the CK mixed micelles significantly inhibited tumor growth, thereby decreasing tumor volume at the end of the experiment as compared with that in the control mice. Histological analysis confirmed the antitumor effect with low toxicity. CONCLUSION: The PC/DP micellar system was an effective drug delivery system for CK in tumor therapy.