Co-delivery of Docetaxel and Resveratrol by liposomes synergistically boosts antitumor efficiency against prostate cancer

Eur J Pharm Sci. 2022 Jul 1:174:106199. doi: 10.1016/j.ejps.2022.106199. Epub 2022 May 6.

Abstract

Combination therapy is frequently used in cancer treatments. Delivery of combined anticancer agents loaded in a nanocarrier would be a promising option for combination therapy. Here, we designed PEGylated nano-liposomes for co-delivery Docetaxel (Doc) and Resveratrol (Res) to evaluate antitumor efficiency of the combined drugs in prostate cancer. The average diameter of the liposomes was 99.67 nm with a spheral-like shape. Drug release studies showed that both drugs could synchronously leak from the liposomes in a sustained release behavior. Cellular uptake results demonstrated that liposomes could effectively deliver more cargos into cells than other formulations. Moreover, co-loaded liposomes with Doc/Res in a molar ratio of 1:2 exhibited significantly higher cytotoxicity than a mixed solution containing both drugs on cancer cells. In the study of caspase 3, we found that the combination of Doc and Res could significantly increase the activity of caspase 3 enzyme compared with Doc alone. Animal studies revealed that co-encapsulated Doc/Res in liposomes predominantly inhibited tumor growth in PC3 bearing Balb/c nude mice, as evidenced by a change in cell proliferation and apoptosis parameters. Importantly, little toxicities and prolonged survival time were observed in mice treated with liposome-loaded Doc/Res than control group exposed to liposome-free Doc/Res. These results provided evidence that loading of Doc/Res in a nano-liposome is an efficient delivery formulation for synergistic treating prostate cancer.

Keywords: Co-loaded liposomes; Combination therapy; Docetaxel; Resveratrol; Synergistic effect.

MeSH terms

  • Animals
  • Antineoplastic Agents* / therapeutic use
  • Caspase 3
  • Cell Line, Tumor
  • Docetaxel
  • Drug Delivery Systems
  • Humans
  • Liposomes
  • Male
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms* / drug therapy
  • Resveratrol

Substances

  • Antineoplastic Agents
  • Liposomes
  • Docetaxel
  • Caspase 3
  • Resveratrol