title: Soluplus micelles for improving the oral bioavailability of scopoletin and their hypouricemic effect in vivo.
abstract: 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 Cmaxof 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.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D033461:Hyperuricemia / Q000188:drug therapy*; D008297:Male; D008813:Mice, Inbred ICR; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012603:Scopoletin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D008823:Micelles; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D012603:Scopoletin