Development of Mixed Micelles for Enhancing Fenretinide Apparent Solubility and Anticancer Activity Against Neuroblastoma Cells.

INTRODUCTION/OBJECTIVES: The purpose of the study was to evaluate the suitability of mixed micelles prepared with D-α-tocopheryl polyethylene glycol succinate (TPGS) and 1,2- distearoyl-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) to encapsulate the poorly soluble anticancer drug fenretinide (4-HPR).

METHODS

After assaying the solubilization ability of the surfactants by the equilibrium method, the micelles were prepared using the solvent casting technique starting from different 4-HPR:TPGS: DSPE-PEG w/w ratios. The resulting formulations were investigated for their stability under storage conditions and upon dilution, modelling the reaching of physiological concentrations after intravenous administration. The characterization of micelles included the determination of DL%, EE %, particle size distribution, Z-potential, and thermal analysis by DSC. The cytotoxicity studies were performed on HTLA-230 and SK-N-BE-2C neuroblastoma cells by the MTT essay.

RESULTS

The colloidal dispersions showed a mean diameter of 12 nm, negative Zeta potential, and a narrow dimensional distribution. 4-HPR was formulated in the mixed micelles with an encapsulation efficiency of 88% and with an increment of the apparent solubility of 363-fold. The 4-HPR entrapment remained stable up to the surfactants' concentration of 2.97E-05 M. The loaded micelles exhibited a slow-release behaviour, with about 28% of the drug released after 24 h. On the most resistant SK-N-BE-2C cells, the encapsulated 4-HPR was significantly more active than free 4-HPR in reducing cell viability.

CONCLUSION

Loaded micelles demonstrated their suitability as a new adjuvant tool potentially useful for the treatment of neuroblastoma.