Development of TPGS/F127/F68 mixed polymeric micelles: Enhanced oral bioavailability and hepatoprotection of syringic acid against carbon tetrachloride-induced hepatotoxicity

Food Chem Toxicol. 2020 Mar:137:111126. doi: 10.1016/j.fct.2020.111126. Epub 2020 Jan 16.

Abstract

Syringic acid (SA), a natural polyphenol found in fruits and vegetables, is claimed to show notable hepatoprotection. Nevertheless, low solubility and bioavailability hamper the application of SA. This study aimed to investigate the potential of TPGS/F127/F68 mixed polymeric micelles as a sustained and liver-targeting nanocarrier for SA. Herein, the prepared SA-loaded TPGS/F127/F68 mixed polymeric micelles (SA-TPGS-Ms) were spherically-shaped and homogeneously-distributed nanoparticles with high entrapment efficiency (94.67 ± 2.05%) and sustained release. Besides, in-vitro cell culture studies revealed that SA-TPGS-Ms substantially promoted cellular uptake with excellent biocompatibility. After oral administration, SA-TPGS-Ms demonstrated an increased bioavailability (2.3-fold) and delayed in-vivo elimination compared with the free SA. Furthermore, the alleviation of oxidative stress and amelioration of hepatic injury in CCl4-induced hepatotoxicity mice further demonstrated the excellent hepatoprotection of SA-TPGS-Ms. Collectively, SA-TPGS-Ms could be a promising nanocarrier for the utilization of SA in functional foods, with enhanced bioavailability and hepatoprotection.

Keywords: Carbon tetrachloride; Hepatoprotection; Mixed micelles; Oral bioavailability; Sustained release; Syringic acid.

Publication types

  • Evaluation Study

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Carbon Tetrachloride / toxicity*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Drug Carriers / chemistry
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods*
  • Gallic Acid / administration & dosage
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / chemistry
  • Gallic Acid / pharmacokinetics
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Micelles
  • Nanoparticles / chemistry
  • Oxidative Stress / drug effects
  • Polyethylene Glycols / chemistry
  • Polyethylenes / chemistry
  • Polypropylenes / chemistry
  • Propylene Glycols / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Vitamin E / chemistry

Substances

  • Drug Carriers
  • Micelles
  • PEO-PPO-PEO
  • Polyethylenes
  • Polypropylenes
  • Propylene Glycols
  • Vitamin E
  • Polyethylene Glycols
  • Gallic Acid
  • UCON 50-HB-5100
  • Carbon Tetrachloride
  • syringic acid
  • tocophersolan