Formulation and optimization of glycyrrhetinic acid-modified pH-sensitive curcumin liposomes for anti-hepatocellular carcinoma

In order to enhance the therapeutic value of curcumin in liver cancer treatment, glycyrrhetinic acid-modified pH-sensitive curcumin liposomes (GA-pH-Lip@Cur) was developed.GA-pH-Lip@Cur was prepared using a thin film dispersion ultrasonication method, and the optimal formulation process was selected through single-factor experiments and a Box-Behnken design-response surface methodology. The liposomes were evaluated for their morphological appearance, particle size, <i>in vitro</i> release at different pH levels, and biocompatibility. The anti-tumor effect of GA-pH-Lip@Cur was assessed using cell viability assays (CCK-8). The <i>in vivo</i> hepatic targeting and anti-liver tumor efficacy of GA-pH-Lip@Cur were evaluated through pharmacokinetic and pharmacological experiments. The results indicated that optimized GA-pH-Lip@Cur exhibited uniform particle size distribution, good stability, pH-sensitive <i>in vitro</i> release with sustained behavior. Compared to conventional liposomes, GA-pH-Lip@Cur showed prolonged average retention time <i>in vivo</i> and significantly increased curcumin distribution in liver tissues, indicating excellent liver targeting. Both <i>in vitro</i> and <i>in vivo</i> evaluations demonstrated the effectiveness of GA-pH-Lip@Cur in inhibiting liver cancer cell proliferation and suppressing liver tumor growth in tumor-bearing mice. In conclusion, GA-pH-Lip@Cur, by leveraging the acidic tumor microenvironment and overexpression of glycyrrhetinic acid receptors in liver cells, encapsulates curcumin to improve its bioavailability, and target its delivery to the liver tumor sites.