Soluplus micelles for improving the oral bioavailability of scopoletin and their hypouricemic effect in vivo  

作　　者：Ying-chun ZENG Sha LI Chang LIU Tao GONG Xun SUN Yao FU Zhi-rong ZHANG 

机构地区：[1]Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, SichuanUniversity, Chengdu 610041, China

出　　处：《Acta Pharmacologica Sinica》2017年第3期424-433,共10页中国药理学报（英文版）

基　　金：Acknowledgements This work was funded by the National S＆T Major Project of China （No 2011ZX09310-002） and the National Natural Science Foundation of China （No 81130060）.

摘　　要：Scopoletin is an active coumarin possessing a variety of pharmacological activities, including anti-hyperuricemic effect, but with poor solubility. To improve its oral bioavailability, we attempted to encapsulate scopoletin into Soluplus micelles （Soluplus-based scopoletin micelles, Sco-Ms） and evaluated the hypouricemic action of Sco-Ms. Sco-Ms were prepared using a thin-film hydration method. Sco-Ms displayed near spherical shapes with an average size of 59.4±2.4 nm （PDI=0.08＋0.02）. The encapsulation efficiency of scopoletin was 87.3%±1.5% with a loading capacity of 5.5%±0.1%. Sco-Ms were further characterized using transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared techniques and scanning electron microscopy. After oral administration in rats, Sco-Ms exhibited significantly improved absorption in each intestinal segment compared to free scopoletin, with the duodenum and jejunum being the main absorption regions. In rats administered Sco-Ms （at an equivalent dose of free scopoletin of 100 mg/kg, po）, the AUC0-∞ and Cm,x of Sco-Ms were 4.38- and 8.43-fold, respectively, as large as those obtained following administration of free scopoletin. After oral administration in rats, Sco-Ms did not alter the tissue distributions of scopoletin, but significantly increased the scopoletin levels in the liver. In potassium oxonate-induced hyperuricemic mice, oral administration of Sco-Ms （at an equivalent dose of free scopoletin of 300 mg/kg） reduced the serum uric acid concentration to the normal level. The results suggest that Soluplus-based micelle system greatly improves the bioavailability of poorly water-soluble drugs, such as scopoletin, and represents a promising strategy for their oral delivery.Scopoletin is an active coumarin possessing a variety of pharmacological activities, including anti-hyperuricemic effect, but with poor solubility. To improve its oral bioavailability, we attempted to encapsulate scopoletin into Soluplus micelles （Soluplus-based scopoletin micelles, Sco-Ms） and evaluated the hypouricemic action of Sco-Ms. Sco-Ms were prepared using a thin-film hydration method. Sco-Ms displayed near spherical shapes with an average size of 59.4±2.4 nm （PDI=0.08＋0.02）. The encapsulation efficiency of scopoletin was 87.3%±1.5% with a loading capacity of 5.5%±0.1%. Sco-Ms were further characterized using transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared techniques and scanning electron microscopy. After oral administration in rats, Sco-Ms exhibited significantly improved absorption in each intestinal segment compared to free scopoletin, with the duodenum and jejunum being the main absorption regions. In rats administered Sco-Ms （at an equivalent dose of free scopoletin of 100 mg/kg, po）, the AUC0-∞ and Cm,x of Sco-Ms were 4.38- and 8.43-fold, respectively, as large as those obtained following administration of free scopoletin. After oral administration in rats, Sco-Ms did not alter the tissue distributions of scopoletin, but significantly increased the scopoletin levels in the liver. In potassium oxonate-induced hyperuricemic mice, oral administration of Sco-Ms （at an equivalent dose of free scopoletin of 300 mg/kg） reduced the serum uric acid concentration to the normal level. The results suggest that Soluplus-based micelle system greatly improves the bioavailability of poorly water-soluble drugs, such as scopoletin, and represents a promising strategy for their oral delivery.

关 键 词：SCOPOLETIN Soluplus micelles oral bioavailability PHARMACOKINETICS tissue distribution hyperuricemic mice 

分 类 号：R[医药卫生]