Preparation, Characterisation and In Vivo Evaluation of Silybin Nanoparticles for the Treatment of Liver Fibrosis

Purpose: To formulate and characterize nanoparticles containing silybin, and evaluate their activity against carbon tetrachloride (CCl₄)-induced liver toxicity.
Methods: Silybin nanoparticles were formulated by o/w emulsion solvent evaporation technique using poly-ε-caprolactone as polymer. Four different nanoparticle formulations (NP₁, NP₂, NP₃ and NP₄) were prepared by varying the drug/polymer ratio. The particles were characterized for particle size, drug content and in vitro drug release. The pharmacokinetics and pharmacodynamics of the silybin formulations in male Wistar rats were evaluated following i.v. administration, using silybin solution as reference. The hepatoprotective activity of the formulations was also determined in a CCl₄-treated rat model.
Results: Silybin nanoparticles were successfully prepared using o/w emulsion solvent evaporation technique. The nanoparticles sustained the release of the drug both in vitro and in vivo for up to 10 days and offered better pharmacokinetic properties than the free drug itself. Intravenous nanoparticulate administration reversed serum liver enzyme levels by 95 % compared to only 50 % for the drug solution.
Conclusion: The developed silybin nanoparticles showed superior pharmacokinetic properties and hepatoprotective activity to silybin solution.

Keywords
Silybin, Nanoparticles, Pharmacokinetics, Pharmacodynamics, Hepatoprotective activity.