Characterization of nano oxaliplatin prepared by novel Fat Employing Supercritical Nano System, the FESNS^®

Abstract

Background: Oxaliplatin has long been used for the treatment of colorectal cancer via intra-venous infusion. In order to improve patient compliance, a solid dosage form for oral administration of oxaliplatin was prepared as nano-sized particles.

Method: Nano oxaliplatin was prepared employing Fat Employing Supercritical Nano System (FESNS^®) with Supercritical Fluid (SCF) apparatus by using myristyl alcohol as solvent. Morphology of nano oxaliplatin was examined by Scanning Electron Microscopy (SEM), and the particle size and zeta potential were confirmed with Dynamic Light Scattering (DLS). To characterize the nano oxaliplatin particles, solubility rate and in vitro efficacy study (MTS growth inhibition assay) were investigated compared to crude oxaliplatin as reference.

Result: FESNS^® provided reproducible nano oxaliplatin with high manufacturing yield (> 95%). SEM images showed that the particle size distribution of nano oxaliplatin ranged between 20 and 400 nm with the medium particle sizes (d₅₀) of about 164 nm determined by DLS. Pertaining to the long-term stability, no recrystallization of the nano oxaliplatin was observed with negative zeta potential in the state of solution. Nano oxaliplatin was completely dissolved within a couple of minutes in pH 4.0 and pH 6.8 buffer solutions while crude oxaliplatin took a couple of hours to go into solution. In case of MTS growth inhibition assay, the average concentration required to inhibit 50% of cell growth (GI₅₀) of nano oxaliplatin was decreased by about 45% in comparison to the crude oxaliplatin.

Conclusion: These results lead us to conclude that nano oxaliplatin would have a great potential for the improvement of efficacy and toxicity in human colorectal cancer treatment compared to the crude oxaliplatin.

Keywords::

• FESNS^®
• nano oxaliplatin
• supercritical fluid
• in vitro efficacy

Acknowledgments

The authors thank Biosynectics for their technical support and advice for this project.

Declaration of interest

This work was supported by a grant from the Ministry of Health & Welfare of the Korean Government (A084141). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.