Annonaceous acetogenins nanosuspensions stabilized by poloxamer 188: Preparation, properties and in vivo evaluation

Abstract

Annonaceous acetogenins (ACGs) have extensive antitumor activities. However, the poor solubility limits their clinical application. In this research, ACGs nanosuspensions (ACGs-NSps) were prepared by antisolvent-precipitation method using poloxamer 188 (P188) as stabilizer. The prepared P188-ACGs-NSps had a mean particle size of 115.9 nm, the polydispersity index (PDI) was 0.208. P188-ACGs-NSPs were stable in different physiological media and displayed a sustained drug release behavior until 144 h.Lyophilized P188-ACGs-NSps using 0.5% glucose as lyoprotectant were stable for long-term storage. P188-ACGs-NSps significantly enhanced the cytotoxicity against 4T1 and HeLa cell lines compared with ACGs solution (IC50:1.426 ± 0.308 vs.3.106 ± 0.691, IC50: 0.718 ± 0.1934 vs. 1.521 ± 0.1992). In vivo antitumor study indicated that P188-ACGs-NSps exhibited great antitumor efficacy against 4T1 tumor with an inhibition rate of 63% at a low intravenous injection dose of 0.4 mg/kg. P188-ACGs-NSps seem to be a promising drug delivery system for ACGs to improve their solubility that can be applied in clinic in the future.