Annonaceous acetogenins (ACGs) nanosuspensions based on a self-assembly stabilizer and the significantly improved anti-tumor efficacy

Annonaceous acetogenins (ACGs) have exhibited antitumor activity against various cancers. However, these substances' poor solubility has limited clinical applications. In this study, hydroxypropyl-betacyclodextrin (HP-beta-CD) and soybean lecithin (SPC) were self-assembled into an amphiphilic complex. ACGs nanosuspensions (ACGs-NSps) were prepared with a mean particle size of 144.4 nm, a zeta potential of -22.9 mV and a high drug payload of 46.17% using this complex as stabilizer. The ACGs-NSps demonstrated sustained release in vitro and good stability in plasma as well as simulated gastrointestinal fluid, and met the demand of both intravenous injection and oral administration. The ACGs-NSps demonstrated significantly increased cytotoxicity against Hela and HepG2 cancer cell lines compared to ACGs in solution (in vitro cytotoxicity assay). An in vivo study with H22-tumor bearing mice demonstrated that nanosuspensions significantly improved ACGs' antitumor activity. When orally administered, ACGs-NSps achieved a similar tumor inhibition rate at 1/10th the dose of ACGs in an oil solution (47.94% vs. 49.74%, p > 0.05). Improved therapeutic efficacy was further achieved when the ACGs-NSps were intravenously injected into mice (70.31%). With the help of nanosuspension technology, ACGs may be an effective antitumor drug for clinic use. (C) 2016 Elsevier B.V. All rights reserved.