title: Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation.
abstract: BACKGROUND
  The purpose of this study was to develop a novel silymarin-loaded solid nanoparticle system with enhanced oral bioavailability and an ability to provide excellent hepatic protection for poorly water-soluble drugs using Shirasu porous glass (SPG) membrane emulsification and a spray-drying technique.
  
  
  METHODS
  A silymarin-loaded liquid nanoemulsion was formulated by applying the SPG membrane emulsification technique. This was further converted into solid state nanosized particles by the spray-drying technique. The physicochemical characteristics of these nanoparticles were determined by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. Their dissolution, bioavailability, and hepatoprotective activity in rats were assessed by comparison with a commercially available silymarin-loaded product.
  
  
  RESULTS
  Formulation of a silymarin-loaded nanoemulsion, comprising silymarin, castor oil, polyvinylpyrrolidone, Transcutol HP, Tween 80, and water at a weight ratio of 5/3/3/1.25/1.25/100 was accomplished using an SPG membrane emulsification technique at an agitator speed of 700 rpm, a feed pressure of 15 kPa, and a continuous phase temperature of 25°C. This resulted in generation of comparatively uniform emulsion globules with a narrow size distribution. Moreover, the silymarin-loaded solid nanoparticles, containing silymarin/castor oil/polyvinylpyrrolidone/Transcutol HP/Tween 80 at a weight ratio of 5/3/3/1.25/1.25, improved about 1,300-fold drug solubility and retained a mean size of about 210 nm. Silymarin was located in unaltered crystalline form in the nanoparticles. The drug dissolved rapidly from the nanoparticles, reaching nearly 80% within 15 minutes, indicating three-fold better dissolution than that of the commercial product. Further, the nanoparticles showed a considerably shorter time to peak concentration, a greater area under the concentration-time curve, and a higher maximum concentration of silymarin compared with the commercial product (P < 0.05). In particular, the area under the concentration-time curve of the drug provided by the nanoparticles was approximately 1.3-fold greater than that of the commercial product. In addition, the silymarin-loaded nanoparticles significantly reduced carbon tetrachloride-induced hepatotoxicity, indicating improved bioactivity compared with silymarin powder and the commercial product.
  
  
  CONCLUSIONS
  Silymarin-loaded nanoparticles developed using SPG membrane emulsification and spray-drying techniques could be a useful system for delivery of poorly water-soluble silymarin while affording excellent hepatic protection.
authors.affiliation: College of Pharmacy, Yeungnam University, Dae-Dong, Gyongsan, Ansan, South Korea.
authors.forename: Kwan Yeol
authors.initials: KY
authors.lastname: Yang
authors.forename: Du Hyeong
authors.initials: du H
authors.lastname: Hwang
authors.forename: Abid Mehmood
authors.initials: AM
authors.lastname: Yousaf
authors.forename: Dong Wuk
authors.initials: DW
authors.lastname: Kim
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Shin
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000818:Animals; D001682:Biological Availability; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D003890:Desiccation / Q000379:methods; D004058:Diffusion; D004655:Emulsions / Q000138:chemical synthesis; D008297:Male; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D020011:Protective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012838:Silymarin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D004655:Emulsions; D053769:Nanocapsules; D020011:Protective Agents; D012838:Silymarin; D002251:Carbon Tetrachloride
keywords: Shirasu porous glass membrane; enhanced oral bioavailability; hepatoprotective activity; nanoparticle; silymarin
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