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Intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway

Authors Wang J, Zhu RR, Sun XY, Zhu YJ, Liu H, Wang SL

Received 14 March 2014

Accepted for publication 27 April 2014

Published 20 August 2014 Volume 2014:9(1) Pages 3987—3998

DOI https://doi.org/10.2147/IJN.S64103

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Jiao Wang,1 Rongrong Zhu,1 Xiaoyu Sun,1 Yanjing Zhu,1 Hui Liu,2 Shi-Long Wang1

1Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China; 2Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People’s Republic of China

Abstract: The objective of this study was to prepare and characterize etoposide (VP16)-loaded solid lipid nanoparticles (SLNs) and evaluate their antitumor activity in vitro. VP16-SLNs were prepared using emulsification and low-temperature solidification methods. The physicochemical properties of the VP16-SLNs were investigated by particle-size analysis, zeta potential measurement, drug loading, drug entrapment efficiency, stability, and in vitro drug-release behavior. In contrast to free VP16, the VP16-SLNs were well dispersed in aqueous medium, showing a narrow size distribution at 30–50 nm, a zeta potential value of −28.4 mV, high drug loading (36.91%), and an ideal drug entrapment efficiency (75.42%). The drug release of VP16-SLNs could last up to 60 hours and exhibited a sustained profile, which made it a promising vehicle for drug delivery. Furthermore, VP16-SLNs could significantly enhance in vitro cytotoxicity against SGC7901 cells compared to the free drug. Furthermore, VP16-SLNs could induce higher apoptotic rates, more significant cell cycle arrest effects, and greater cellular uptake in SGC7901 cells than free VP16. Moreover, results demonstrated that the mechanisms of VP16-SLNs were similar to those claimed for free VP16, including induction of cellular apoptosis by activation of p53, release of cytochrome c, loss of membrane potential, and activation of caspases. Thus, these results suggested that the SLNs might be a promising nanocarrier for VP16 to treat gastric carcinoma.

Keywords: sustained profile, gastric carcinoma, SLNs, cytochrome c, caspases

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