title: Enhanced oral bioavailability of silymarin using liposomes containing a bile salt: preparation by supercritical fluid technology and evaluation in vitro and in vivo.
abstract: The aim of this investigation was to develop a procedure to improve the dissolution and bioavailability of silymarin (SM) by using bile salt-containing liposomes that were prepared by supercritical fluid technology (ie, solution-enhanced dispersion by supercritical fluids [SEDS]). The process for the preparation of SM-loaded liposomes containing a bile salt (SM-Lip-SEDS) was optimized using a central composite design of response surface methodology with the ratio of SM to phospholipids (w/w), flow rate of solution (mL/min), and pressure (MPa) as independent variables. Particle size, entrapment efficiency (EE), and drug loading (DL) were dependent variables for optimization of the process and formulation variables. The particle size, zeta potential, EE, and DL of the optimized SM-Lip-SEDS were 160.5 nm, -62.3 mV, 91.4%, and 4.73%, respectively. Two other methods to produce SM liposomes were compared to the SEDS method. The liposomes obtained by the SEDS method exhibited the highest EE and DL, smallest particle size, and best stability compared to liposomes produced by the thin-film dispersion and reversed-phase evaporation methods. Compared to the SM powder, SM-Lip-SEDS showed increased in vitro drug release. The in vivo AUC(0-t) of SM-Lip-SEDS was 4.8-fold higher than that of the SM powder. These results illustrate that liposomes containing a bile salt can be used to enhance the oral bioavailability of SM and that supercritical fluid technology is suitable for the preparation of liposomes.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yang
authors.affiliation: School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Yongtai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Beilei
authors.initials: B
authors.lastname: Dang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Nianping
authors.initials: N
authors.lastname: Feng
mesh_terms: D000284:Administration, Oral; D001647:Bile Acids and Salts / Q000737:chemistry*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D008081:Liposomes; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D011312:Pressure; D012838:Silymarin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D001647:Bile Acids and Salts; D008081:Liposomes; D010743:Phospholipids; D012838:Silymarin
keywords: bile salt; bioavailability; liposomes; silymarin; solution-enhanced dispersion by supercritical fluids