Preparation, characterization, and pharmacokinetics study of a novel genistein-loaded mixed micelles system

Abstract

Genistein (GEN), is a natural dietary isoflavone, has been reported to show anticancer activities. However, its poor aqueous solubility and oral bioavailability limit its clinical application. We designed a novel genistein-loaded mixed micelles (GEN-M) system composed of Soluplus^® and Vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared by organic solvent evaporation aimed to overcome the challenges of GEN’s poor solubility and then further improve its oral bioavailability. The optimized, spherical-shaped GEN-M was obtained at a ratio of 10:1 (Soluplus^®:TPGS). The mean particle size of GEN-M was 184.7 ± 2.8 nm, with a narrow polydispersity index (PDI) of 0.162 ± 0.002. The zeta potential value of GEN-M was −2.92 ± 0.01 mV. The micelles solutions was transparent with blue opalescence has high the entrapment efficiency (EE) and drug loading (DL) of 97.12 ± 2.11 and 3.87 ± 1.26%, respectively. GEN-M was demonstrated a sustained release behavior when formed micelles shown in drug release in vitro. The solubility of GEN in water increased to 1.53 ± 0.04 mg/mL after encapsulation. The permeability of GEN across a Caco-2 cell monolayer was enhanced, and the pharmacokinetics study of GEN-M showed a 2.42-fold increase in relative oral bioavailability compared with free GEN. Based on these findings, we conclude that this novel nanomicelles drug delivery system could be leveraged to deliver GEN and other hydrophobic drugs.

Keywords:

• Genistein
• micelles
• Soluplus^®
• TPGS
• oral bioavailability

Disclosure statement

The authors declare no competing financial interest. All authors have contributed to the research.

Additional information

Funding

This study was financially supported by National Nature Science Foundation of China [Grant No. 81202929 and 81302688]; ‘Six Major Talent Peak Project’ of Jiangsu province (2015-YY-011).