Background: Vorinostat (VRS), a histone deacetylases inhibitor, has significant cytotoxic potential in a large number of human cancer cell lines.
Objective: To clarify its promising anticancer potential and to improve its drawback related to physical properties and in vivo performance of VRS.
Methods: VRS was successfully incorporated into nanostructured lipid carriers (NLCs) by the hot microemulsion method using sonication following a homogenization technique.
Results: After the optimization process, VRS-loaded NLCs (VRS-NLCs) were obtained as ideal quality nanoparticles with a spherical shape, small size (∼150 nm), negative charge (∼-22 mV), and narrow size distribution. In addition, the high entrapment efficiency (∼99%) and sustained drug release profile were recorded. Cytotoxicity study in three different cell lines (A549, MCF-7, and SCC-7) demonstrated higher cytotoxicity of VRS-NLCs than free drug. Finally, the AUC of VRS (118.16 ± 17.35 µgh/mL) was enhanced ∼4.4 times compared with that of free drug (27.03 ± 3.25 µgh/mL).
Conclusion: These results suggest the potential of NLCs as an oral delivery system for enhancement of cellular uptake, in vitro cytotoxicity in cancer cell lines and the oral bioavailability of VRS.
Keywords: Histone deacetylases inhibitor; nanostructured lipid carriers; oral bioavailability; vorinostat.