Galactosylated gelatin nanovectors of doxorubicin inhibit cell proliferation and induce apoptosis in hepatocarcinoma cells

Anticancer Drugs. 2012 Sep;23(8):836-45. doi: 10.1097/CAD.0b013e328351424f.

Abstract

We have synthesized and characterized doxorubicin (DOX)-loaded galactosylated gelatin nanovectors using in vitro and in vivo for targeting liver cells including hepatocarcinoma cells. Galactosylated and nongalactosylated gelatin nanovectors (GL-GN-DOX and GN-DOX) were spherical in shape and had mean sizes of about 95.1 and 88.3 nm, respectively. In-vitro release of DOX from nanovectors followed first-order kinetics and was pH dependent. Galactosylated formulation released 95.2% of DOX compared with 86.6% by nongalactosylated formulation at pH 5.8. However, the release rate was suppressed at pH 7.4. Further, we showed that GL-GN-DOX had greater growth inhibitory effect on HepG2 in terms of low inhibitory concentration (IC(50); 0.35 µg/ml) compared with GN-DOX (0.75 µg/ml) and induced caspase-3-mediated apoptosis in HepG2 cells. This might be due to efficient internalization of galactosylated nanovectors by HepG2 cells compared with unmodified formulation. Pharmacokinetic and biodistribution analyses show that galactosylated formulation deposits 24.5 µg/g of DOX in targeted tissue (liver) in comparison with heart (0.3 µg/g) at a single dose of 10 mg/kg. These results suggest that DOX-loaded galactosylated gelatin nanovectors warrant future in-depth antitumor study to scale-up technology and may be used for the management of hepatocarcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems
  • Galactose / chemistry
  • Gelatin / chemistry
  • Hep G2 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Inhibitory Concentration 50
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Nanospheres
  • Particle Size
  • Tissue Distribution

Substances

  • Antibiotics, Antineoplastic
  • Doxorubicin
  • Gelatin
  • Caspase 3
  • Galactose