Abstract: Objective To prepare an adriamycin-glycyrrhizin molecular complex (ADR-GL complex) using glycyrrhizin (GL, a component in traditional Chinese drug) as the carrier and assess the solubility and anti-tumor activity of the complex. Methods Dried solid products of ADR-GL complex with different molar ratios of ADR and GL (2∶1, 1∶1, and 1∶2) were prepared by rotary steaming and characterized using FT-IR and DSC. The products were dissolved in pH7.4 phosphate buffer, sonicated overnight, and centrifuged to obtain saturated ADR-GL complex solution, and ADR solubility was determined using high-performance liquid chromatography (HPLC). The cytotoxicity of ADR and ADR-GL complex was evaluated in HepG2 cells by assessing the cell viability using MTT assay. Breast cancer MDA-MB-231 cells were treated with ADR-GL complex and the proportion of CD44 + cells in the total cells was measured by flow cytometry to evaluate the anti- tumor activity of the complex. Results FT-IR spectrum of solid ADR-GL complex did not show the absorption peak of adriamycin at 1525 cm-1 , and an intense absorption peak of ADR-GL occurred at 86 ℃ in DSC, indicating that ADR molecules were encapsulated by GL, the giving rise to the new form of ADR-GL molecular complex. The solubility of ADR in pH7.4 phosphate buffer in the control group was 0.844±0.011 mmol/L, significantly different from that in ADR-GL complex group (P<0.05). The ADR-GL complex with an ADR to GL ratio of 1∶2 showed the highest ADR solubility (5.562 ± 0.049 mmol/L), which was 6.3 times that of the control sample. The ADR-GL complex and ADR showed similar inhibitory effects on HepG2 cells and the negative stemness population of MDA-MB-231 stem cells. Conclusion The ADR-GL complex does not reduce the antitumor activity of ADR and may serve potentially as a safe and novel drug delivery system.

Key words: adriamycin; glycyrrhizin; molecular complex; anti-tumor activity