Abstract
Background: Augmentation of simvastatin (SMV) cytotoxicity in breast carcinoma cell lines MCF-7, by: improvement of cellular uptake and loading on alpha lipoic acid (ALA).
Methods: In this study, SMV was loaded on ALA nanoparticles and characterized for surface morphology, SMV entrapment efficiency percent (%EE), zeta potential and release profile. Cellular viability, morphology and uptake and DNA fragmentations were analyzed as a hallmark of cellular apoptosis.
Results: TEM images demonstrated spherical nanoparticles with particle size 104.7 +/- 5.5 nm, SMV %EE was 95.8 +/- 2.1% with a zeta potential - 23.6 +/- 5.4 mV, and release properties were significantly enhanced. IC50 was decreased to 22.2 +/- 2.4 mu M while raw SMV was 49.3 +/- 6.6 mu M. Cellular uptake of SMV-ALA nanoparticles was increased by about 3- and 2-folds after 2 and 4h, respectively. DNA fragments confirmed the apoptosis property of ALA, which is associated with SMV cytotoxicity.
Conclusion: This study suggests evidence that SMV loaded on ALA nanoparticles increases the MCF-7 cellular uptake and cytotoxic effects induced by SMV as revealed by significantly enhanced cell death rates in MCF-7 cells. These findings demonstrate that ALA induces cell death, which makes the combination a candidate for tumor therapy.