Silymarin-Loaded Eudragit Nanoparticles: Formulation, Characterization, and Hepatoprotective and Toxicity Evaluation

AAPS PharmSciTech. 2017 Nov;18(8):3076-3086. doi: 10.1208/s12249-017-0799-9. Epub 2017 May 17.

Abstract

The objectives of this study were to formulate, characterize silymarin-loaded Eudragit nanoparticles (SNPs) and evaluate their hepatoprotective and cytotoxic effects after oral administration. SNPs were prepared by nanoprecipitation technique and were evaluated for particle size, entrapment efficiency, TEM, solid-state characterization, and in vitro drug release. The hepatoprotective activity was evaluated after oral administration of selected SNPs in carbon tetrachloride-intoxicated rats. Potential in vivo acute cytotoxicity study was also assessed. The selected SNPs contained 50 mg silymarin and 50 mg Eudragit polymers (1:1 w/w Eudragit RS 100 & Eudragit LS 100). Morphology of the selected SNPs (particle size of 84.70 nm and entrapment efficiency of 83.45% with 100% drug release after 12 h) revealed spherical and uniformly distributed nanoparticles. DSC and FT-IR studies suggested the presence of silymarin in an amorphous state and absence of chemical interaction. The hepatoprotective evaluation of the selected SNPs in CCl4-intoxicated rats revealed significant improvement in the activities of different biochemical parameters (P ≤ 0.01) compared to the marketed product. The histopathological studies suggested that the selected SNPs produced better hepatoprotective effect in CCl4-intoxicated rats compared with the commercially marketed product. Toxicity study revealed no evident toxic effect for blank or silymarin-loaded nanoparticles at the dose level of 50 mg/kg body weight. The obtained results suggested that the selected SNPs were safe and potentially offered enhancement in the pharmacological hepatoprotective properties of silymarin.

Keywords: cytotoxicity; eudragit; hepatoprotective; polymeric nanoparticles; silymarin.

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / chemistry
  • Carbon Tetrachloride / toxicity
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Drug Compounding
  • Drug Evaluation, Preclinical / methods
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Particle Size
  • Polymethacrylic Acids / administration & dosage*
  • Polymethacrylic Acids / chemistry
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Silymarin / administration & dosage*
  • Silymarin / chemistry
  • Spectroscopy, Fourier Transform Infrared / methods

Substances

  • Antioxidants
  • Polymethacrylic Acids
  • Silymarin
  • methylmethacrylate-methacrylic acid copolymer
  • Carbon Tetrachloride