Enhanced Anti-Cancer Capability of Ellagic Acid Using Solid Lipid Nanoparticles (SLNs)

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.
The present study proposed to develop solid lipid nanoparticles (SLNs) as a delivery system for improving the anti-cancer capability of EA on prostate cancer cell line.
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).
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.
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.