Permeability, anti-inflammatory and anti-VEGF profiles of steroidal-loaded cationic nanoemulsions in retinal pigment epithelial cells under oxidative stress

Int J Pharm. 2022 Apr 5:617:121615. doi: 10.1016/j.ijpharm.2022.121615. Epub 2022 Feb 22.

Abstract

Age-related macular degeneration (AMD) is defined as a degenerative, progressive and multifactorial disorder that affects the macula with a complex etiology. The retinal pigment epithelium is a monolayer of cells that has the function to separate the surface of the choroid from the neural retina that is involved in the signal transduction leading to vision. The blood-aqueous barrier and the blood retinal barrier limit the permeation of drugs into the retina and thereby reducing their efficacy. Triamcinolone acetonide (TA) is widely used as anti-inflammatory and immunomodulatory drug that promotes the inhibition of the inflammatory processes. The factors that stimulate or inhibit angiogenesis in AMD create a local balance that is responsible for the growth of sub-retinal neovascularization. In AMD, the main angiogenic stimulus is the vascular endothelial growth factor (VEGF). In this work, nanoemulsions with cationic surfactants (mono- and dicationic DABCO and quinuclidine) were produced to deliver TA, and were found to reduce the production of tumor necrosis factor alpha (TNF-α), which stimulates the choroidal neovascularization development by upregulating the VEGF production, and consequently decreased the VEGF levels. Our results support the potential use of mono- and dicationic DABCO and quinuclidine-based cationic nanoemulsions for the delivery of TA in the treatment of AMD.

Keywords: Cationic nanoemulsions; Triamcinolone acetonide; Tumor Necrosis Factor alpha, Choroidal neovascularization; Vascular Endothelial Growth Factor.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Choroidal Neovascularization* / drug therapy
  • Epithelial Cells / metabolism
  • Humans
  • Oxidative Stress
  • Permeability
  • Retinal Pigments / metabolism
  • Retinal Pigments / pharmacology
  • Retinal Pigments / therapeutic use
  • Vascular Endothelial Growth Factor A* / metabolism
  • Vascular Endothelial Growth Factors / metabolism
  • Vascular Endothelial Growth Factors / pharmacology
  • Vascular Endothelial Growth Factors / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Retinal Pigments
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors