Smart liposomal drug delivery for treatment of oxidative stress model in human embryonic stem cell-derived retinal pigment epithelial cells

Int J Pharm. 2018 Sep 5;548(1):62-72. doi: 10.1016/j.ijpharm.2018.05.056. Epub 2018 May 23.

Abstract

Oxidative stress has been implicated in the progression of age-related macular degeneration (AMD). Treatment with antioxidants seems to delay progression of AMD. In this study, we suggested an antioxidant delivery system based on redox-sensitive liposome composed of phospholipids and a diselenide centered alkyl chain. Dynamic light scattering assessment indicated that the liposomes had an average size of 140 nm with a polydispersity index below 0.2. The percentage of encapsulation efficiency of the liposomes was calculated by high-performance liquid chromatography. The carriers were loaded with N-acetyl cysteine as a model antioxidant drug. We demonstrated responsiveness of the nanocarrier and its efficiency in drug delivery in an oxidative stress model of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells. The modeled cells treated with diselenide containing liposomes loaded with 10 mM NAC, showed a better therapeutic effect with a cell metabolic activity of 90%, which was significantly higher compared to insensitive liposomes or NAC treated groups (P < 0.05). In addition, the expression of oxidative-sensitive gene markers in diselenide containing liposomes groups were improved. Our results demonstrated fabricated smart liposomes opens new opportunity for targeted treatment of retinal degeneration.

Keywords: Age macular degeneration; Diselenide; Drug delivery; Human embryonic stem cells; Liposome; Redox sensitive; Retinal pigment epithelium cells.

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Antioxidants / administration & dosage*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Drug Liberation
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Human Embryonic Stem Cells / cytology
  • Humans
  • Liposomes
  • Oxidative Stress
  • Phospholipids / administration & dosage
  • Reactive Oxygen Species / metabolism
  • Retinal Pigment Epithelium / cytology
  • Selenium / administration & dosage*

Substances

  • Antioxidants
  • Liposomes
  • Phospholipids
  • Reactive Oxygen Species
  • Selenium
  • Acetylcysteine