Enhanced Anti-Cancer Capability of Ellagic Acid Using Solid Lipid Nanoparticles (SLNs)
چکیده
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'-6diamidino-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 degrees 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.