Inhibition of orthotopic secondary hepatic carcinoma in mice by doxorubicin-loaded electrospun polylactide nanofibers

Abstract

For the treatment of unresectable liver cancer or for the prevention of post-surgery tumor recurrence, local chemotherapy is probably a good choice. A pilot study was carried out to examine the efficacy of doxorubicin-loaded polylactide electrospun nanofibers (Dox fibers) as a local chemotherapy system against secondary hepatic carcinoma (SHCC). Two orthotopic SHCC models were prepared by injecting murine mammary carcinoma EMT6 cells into the left hepatic lobe and into the portal vein of Balb/c mice, resulting in nodular and diffuse SHCC (NSHCC and DSHCC), respectively. By covering the surface of the NSHCC tumor and by wrapping the whole liver bearing DSHCC with the Dox fiber-mat after explorative laparotomy, the growth of NSHCC was significantly inhibited and median survival time of the mice bearing DSHCC was increased from 14 days to 38 days. Safety study suggested that both blank polylactide fibers (PLLA fibers) and Dox fibers ignited typical inflammatory response in the liver tissue of healthy mice. Acute, reversible impairment on fiber-mat-covered area of hepatic parenchyma was induced by Dox fibers. But neither injury to neighboring liver tissue nor systemic adverse reactions were observed during the experimental period of 42 days. In order to explain the efficacy and safety of Dox fiber treatment, in vivo release and biodistribution of Dox from the fiber-mat was investigated. Dox was rapidly released from the fiber-mat in the first 24 h, preferably localized in fiber-mat-covered area of liver tissue. In conclusion, Dox-loaded polylactide fibers might be used for local chemotherapy of liver cancers.