title: Mixed micelles loaded with silybin-polyene phosphatidylcholine complex improve drug solubility.
abstract: OBJECTIVE
  To prepare a novel formulation of phosphatidylcholine (PC)-bile salts (BS)-mixed micelles (MMs) loaded with silybin (SLB)-PC complex for parenteral applications.
  
  
  METHODS
  SLB-PC-BS-MMs were prepared using the co-precipitation method. Differential scanning calorimetry (DSC) analysis was used to confirm the formation of the complex and several parameters were optimized to obtain a high quality formulation. The water-solubility, drug loading, particle size, zeta potential, morphology and in vivo properties of the SLB-PC-BS-MMs were determined.
  
  
  RESULTS
  The solubility of SLB in water was increased from 40.83 ± 1.18 μg/mL to 10.14 ± 0.36 mg/mL with a high drug loading (DL) of 14.43% ± 0.44% under optimized conditions. The SLB-PC-BS-MMs were observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and showed spherical shapes. The particle size and zeta potential, as measured by photon correlation spectroscopy (PCS), were about 30 ± 4.8 nm and -39 ± 5.0 mV, respectively. In vivo studies showed that incorporation of the SLB-PC complex into PC-BS-MMs led to a prolonged circulation time of the drug.
  
  
  CONCLUSIONS
  This novel formulation appears to be a good candidate for drug substances that exhibit poor solubility for parenteral administration.
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: Rui-ling
authors.initials: RL
authors.lastname: Duan
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Zhi-rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001647:Bile Acids and Salts / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D007262:Infusions, Intravenous; D008823:Micelles; D020944:Silybum marianum / Q000737:chemistry; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D051381:Rats; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012995:Solubility
chemical_list: D000975:Antioxidants; D001647:Bile Acids and Salts; D008823:Micelles; D010713:Phosphatidylcholines; D012838:Silymarin; D000077385:Silybin