Galactosylated nanocrystallites of insoluble anticancer drug for liver-targeting therapy: an in vitro evaluation

Nanomedicine (Lond). 2010 Jun;5(4):589-96. doi: 10.2217/nnm.10.27.

Abstract

Aim: Low solubility in water has become an intrinsic property of many anticancer drugs, which poses a hurdle in the translation from the bench to the clinic. In this study, we developed a facile method to prepare 10-hydroxycamptothecin (HCPT) nanocrystallites and testified their feasibility for liver-targeting therapy.

Materials & methods: HCPT nanocrystallites were prepared under the soft template effect of galactosylated chitosan. The internalization profile, intracellular trafficking, drug activity and cell viability were evaluated by exposing these nanocrystallites to human hepatocellular carcinoma HepG2 cells.

Results: Galactosylated chitosan located on the HCPT nanocrystallites not only stabilized the formulation in aqueous medium, but also enhanced the cellular internalization through an asialoglycoprotein receptor-mediated pathway. These nanocrystallites also exhibited the advantages of nuclear entry and active HCPT delivery, and consequently better anticancer cytotoxicity could be achieved.

Conclusion: These data strongly support the superior properties of galactosylated HCPT nanocrystallites on liver-targeting therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Flow Cytometry
  • Galactose / chemistry*
  • Humans
  • In Vitro Techniques
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • Nanostructures*
  • Solubility

Substances

  • Antineoplastic Agents
  • Galactose