Development of lipid nanoparticles for a histone deacetylases inhibitor as a promising anticancer therapeutic

다국어 초록 (Multilingual Abstract)

<P>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 (similar to 150 nm), negative charge (similar to-22 mV), and narrow size distribution. In addition, the high entrapment efficiency (similar to 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 mu gh/mL) was enhanced similar to 4.4 times compared with that of free drug (27.03 +/- 3.25 mu gh/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.</P>