Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630

Abstract

Xiaoyan Wu,1 Weihong Ge,1 Tengfei Shao,1 Weijun Wu,1 Jian Hou,2 Li Cui,2 Jing Wang,2 Zhenghai Zhang2 1Department of Pharmacy, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, 2Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China Abstract: Biochanin A (BCA), a natural dietary isoflavone, has been reported to show anticancer activities. However, its low biological availability and poor aqueous solubility limit its usefulness as a chemotherapeutic agent. We developed BCA-loaded micelles with Pluronic F127 and Plasdone S630 (BCA-FS). The optimized, spherical-shaped BCA-FS was obtained at a ratio of 1:1 (F127:S630). The particle size was 25.17±1.2 nm, and the zeta potential was −10.9±0.24 mV. BCA solubility in water increased to 5.0 mg/mL after encapsulation, and the drug-loading efficiency was 5.88%±0.76%. In vitro release experiments showed a delayed release of BCA from the mixed micelles. Furthermore, the BCA absorption permeability across a Caco-2 cell monolayer from the apical side to the basolateral side increased by 54% in BCA-FS. A pharmacokinetics evaluation showed a 2.16-fold increase in the relative oral bioavailability of BCA-FS compared with raw BCA, indicating that the mixed micelles may promote absorption in the gastrointestinal tract. A gastrointestinal safety assay was used to assess the reliability and safety of BCA-FS. On the basis of these findings, we conclude that this simple nanomicelle system could be leveraged to deliver BCA and other hydrophobic drugs. Keywords: biochanin A, mixed micelles, oral bioavailability, Pluronic F127, Plasdone S630

Keywords

• Keywords: Biochanin A
• mixed micelles
• oral bioavailability
• Pluronic F127
• Plasdone S630.