Preparation, characterization, and evaluation of the antitumor effect of kaempferol nanosuspensions

Abstract

Abstract Kaempferol (KAE) is a natural flavonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability and suboptimal bioavailability greatly restricted its clinical application of cancer. In order to overcome these shortages and enhance the antitumor effect of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) as stabilizer, screened the optimal preparation process, and investigated the basic properties and the antitumor effect in the study. The results demonstrated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was improved prominently compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable, which had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, higher apoptosis rate and more intracellular ROS production compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity on 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared improved the defect and the antitumor effect of KAE notably, which was a promising nanodrug delivery system for KAE and was expected to become a clinical antitumor drug.