enhanced anti-cancer capability of ellagic acid using solid lipid nanoparticles (slns)

Background: ellagic acid (ea) is a polyphenol, whose anti-cancer properties have been demonstrated in several cancer studies, but the poor water solubility and low bioavailability have limited its therapeutic potential. objectives: the present study proposed to develop solid lipid nanoparticles (slns) as a delivery system for improving the anticancer capability of ea on prostate cancer cell line. methods: ea-loaded slns were prepared by hot homogenization technique and characterized by different techniques. cytotoxicity of ea and ea-loaded slns on prostate cancer cell line (pc3) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (mtt) assay, and nucleus condensation, or chromatin fragmentation (the signs of apoptosis) were studied by 4’-6- diamidino-2-phenylindole (dapi) staining. the expression of b-cell lymphoma 2 (bcl-2) and bcl-2-associated x protein (bax), which are involved in apoptosis, were evaluated by quantitative reverse transcription polymerase chain reaction (qrt-pcr). results: the nanoparticles with appropriate characteristics (particle size of 96 nm and encapsulation efficiency of 88%) were prepared. the in vitro drug release profile showed a burst release in the first hours and followed by a sustained ea release until 72 hours. ea-loaded slns displayed a good stability for 4 weeks of storage at 4 - 8°c. cytotoxicity evaluations demonstrated that ea-loaded slns prevented prostate cancer cells growth in a low ic50 value compared to the ea. the results of qrt-pcr demonstrated that ea causes up-regulation of bax and this regulation intensified when ea was loaded into slns, but there was no punctual correlation between the ea and ea-loaded slns in down-regulation of bcl-2. conclusions: the results strengthen our hope that loading ea into slns could possibly overcome the therapeutic limitations of ea and make it more effective in prostate cancer therapy.