Key result
DOX/GA-GEL-2 micelles boost antitumor activity in mice with a ~50% lower IC50 versus DOX·HCl.
Why the study?
Polymeric micelles with targeting groups have drawn great attention as carriers for drug delivery in hepatocellular carcinoma therapy, but novel carriers with liver-targeting activity need evaluation.
Does DOX/GA-GEL improve antitumor activity compared to DOX·HCl in hepatocellular carcinoma models?
Does DOX/GA-GEL improve antitumor activity compared to DOX·HCl in hepatocellular carcinoma models?
Absolute Event Rate: 0.33% vs 0.66%
DOX-loaded GA-GEL micelles demonstrate liver-targeting capability and enhanced antitumor activity against hepatocellular carcinoma in preclinical models.
GA-GEL micelles warrant further HCC-targeted delivery exploration; leaves open in vivo efficacy and clinical translation.
Hepatocellular carcinoma (HCC) is one of the most prevalent fatal diseases and the incidence of HCC is increasing worldwide. Polymeric micelles with targeting groups have drawn great attention as carriers for drug delivery in HCC therapy. Herein, novel glycyrrhetinic acid modified gelatin (GA-GEL) conjugates with three substitution degrees were synthesized and characterized. Doxorubicin (DOX) was applied as a model drug. DOX-loaded GA-GEL (DOX/GA-GEL) micelles were prepared by an emulsion-solvent evaporation method. The mean diameters of DOX/GA-GEL micelles were in the range of 195–235 nm. The encapsulation efficiency of DOX/GA-GEL micelles was 63.6%–96.2%, and the loading content was 8.3%–12.5%. Drug release from DOX-loaded micelles exhibited a biphasic manner in phosphate buffer solution (PBS) at pH 7.4. DOX/GA-GEL could be efficiently accumulated into human liver cancer HepG2 cells. The IC50 values of DOX/GA-GEL-2 and DOX·HCl in HepG2 cells were 0.33 and 0.66 μg/mL, respectively. In vivo imaging analysis demonstrated that the fluorescence signals of DiR-labeled GA-GEL-2 micelles were mainly distributed in liver and H22 orthotopic tumor, indicating that GA-GEL had the liver-targeting activity. Compared to DOX·HCl, DOX/GA-GEL-2 exhibited better antitumor activity in H22 orthotopic mice. Therefore, these results indicated that GA-GEL could be used as carrier of hydrophobic drug for targeting HCC.
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Fan et al. (2018) studied Hepatocellular carcinoma. Doxorubicin-loaded glycyrrhetinic acid modified gelatin (DOX/GA-GEL) micelles vs. DOX·HCl was evaluated on IC50 in HepG2 cells (μg/mL). DOX/GA-GEL-2 micelles exhibited better antitumor activity in H22 orthotopic mice and a lower IC50 in HepG2 cells (0.33 μg/mL) compared to DOX·HCl (0.66 μg/mL).
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