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, in vitro 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 in vivo 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 in vitro release with sustained behavior. Compared to conventional liposomes, GA-pH-Lip@Cur showed prolonged average retention time in vivo and significantly increased curcumin distribution in liver tissues, indicating excellent liver targeting. Both in vitro and in vivo 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.