Synergistic strategies for enhanced liver cancer therapy with sorafenib/resveratrol PEGylated liposomes in vitro and in vivo

Abstract

This study investigates the therapeutic efficacy of sorafenib (Sr) and resveratrol (Rv) encapsulated in liposomal formulations for liver cancer treatment. In vitro release profiles demonstrated sustained drug release, with 70 % and 56.7 % at intestinal pH of 6.8 and 79.3 % and 74.2 % at gastric pH of 1.2 after 72 h for liposomal (Sr/Rv-Lip) and PEGylated liposomal (Sr/Rv-PEG-Lip) formulations. pH-dependent release patterns highlighted adaptability of these formulations to distinct physiological conditions, crucial for targeted drug delivery. Stability assessments over three months revealed a marginal 8.5 % decrease in Sr/Rv-PEG-Lip encapsulation efficiency, accompanied by nonsignificant alterations in size, zeta potential, and polydispersity index (PDI). These indicate the formulations' capability to preserve physicochemical properties, offering promising enhanced stability for Sr and Rv. In vitro studies demonstrated superior anticancer effects of Sr/Rv-PEG-Lip with an IC50 of 5.1 μM, showing 3.1-fold increased potency, compared to Sr/Rv in H22 cells, demonstrating enhanced cytotoxicity. Sr/Rv-PEG-Lip, compared to Sr/Rv, was 50.5 and 33.1 % more potent in inhibiting proliferation and migration of H22 cells, respectively. The reactive oxygen species (ROS) assay underscored the synergistic potential of Sr and Rv, with PEGylation amplifying oxidative stress induction by 1.4-fold. In vivo, Sr/Rv-PEG-Lip demonstrated superior efficacy in suppressing tumor growth by reducing the tumor volume to 380.4 mm³ and inhibiting the weight gain by 22.7 % with minimal toxicity, demonstrating its translational potential in liver cancer therapy. These findings contribute valuable insights into nanomedicine, suggesting Sr/Rv-loaded PEGylated liposomes as a promising avenue for liver cancer treatment.