Gene delivery in the cornea: in vitro & ex vivo evaluation of solid lipid nanoparticle-based vectors

Nanomedicine (Lond). 2018 Aug 1;13(15):1847-1854. doi: 10.2217/nnm-2018-0112. Epub 2018 May 24.

Abstract

Aim: Inflammation is a process that underlies sight-threatening ocular surface diseases, and gene supplementation with the plasmid that encodes for p-IL10 will allow the sustained de novo synthesis of the cytokine to occur in corneal cells, and provide a long-term anti-inflammatory effect. This work describes the development of solid lipid nanoparticle systems for the delivery of p-IL10 to transfect the cornea.

Results: In vitro, vectors showed suitable features as nonviral vectors (size, ζ-potential, DNA binding, protection and release), and they were able to enter and transfect human corneal epithelial cells. Ex vivo, the vectors were found to transfect the epithelium, the stroma and the endothelium in rabbit corneal explants. Distribution of gene expression within the cell layers of the cornea depended on the composition of the four vectors evaluated.

Conclusion: Solid lipid nanoparticle-based vectors are promising gene delivery systems for corneal diseases, including inflammation.

Keywords: cornea explant; corneal inflammation; corneal transfection; ex vivo; gene delivery; gene supplementation; in vitro; interleukin-10 gene; nonviral vectors; solid lipid nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival
  • Cornea / cytology
  • Cornea / metabolism*
  • Epithelium, Corneal / cytology
  • Epithelium, Corneal / metabolism
  • Eye Diseases / genetics
  • Eye Diseases / therapy*
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Humans
  • Interleukin-10 / genetics*
  • Interleukin-10 / metabolism
  • Lipids / chemistry*
  • Nanoparticles / chemistry*
  • Particle Size
  • Plasmids
  • Rabbits
  • Transfection

Substances

  • Lipids
  • Interleukin-10