Wu Xiaoyan, Ge Weihong, Shao Tengfei, Wu Weijun, Hou Jian, Cui Li, Wang Jing, Zhang Zhenghai
Department of Pharmacy, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School.
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.
Int J Nanomedicine. 2017 Feb 22;12:1475-1483. doi: 10.2147/IJN.S125041. eCollection 2017.
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.
生物chanin A(BCA)是一种天然膳食异黄酮,据报道具有抗癌活性。然而,其低生物利用度和较差的水溶性限制了它作为化疗药物的效用。我们用普朗尼克F127和聚维酮S630开发了载有BCA的胶束(BCA-FS)。以1:1(F127:S630)的比例获得了优化的球形BCA-FS。粒径为25.17±1.2纳米,zeta电位为-10.9±0.24毫伏。包封后BCA在水中的溶解度增加到5.0毫克/毫升,载药效率为5.88%±0.76%。体外释放实验表明BCA从混合胶束中延迟释放。此外,BCA-FS中BCA从顶侧到基底侧跨Caco-2细胞单层的吸收渗透率提高了54%。药代动力学评估表明,与未加工的BCA相比,BCA-FS的相对口服生物利用度提高了2.16倍,表明混合胶束可能促进胃肠道吸收。采用胃肠道安全性试验来评估BCA-FS的可靠性和安全性。基于这些发现,我们得出结论,这种简单的纳米胶束系统可用于递送BCA和其他疏水药物。