Reducible Polyethylenimine Nanoparticles for Efficient siRNA Delivery in Corneal Neovascularization Therapy

Hyounkoo Han, Sohee Son, Sejin Son, Namho Kim, Ji Young Yhee, Jae Hyeop Lee, Jun Sub Choi, Choun Ki Joo, Hohyeon Lee, Duhwan Lee, Won Jong Kim, Sun Hwa Kim, Ick Chan Kwon, Hyuncheol Kim, Kwang Meyung Kim

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10 Citations (Scopus)

Abstract

The aim of this study is to establish the safe and effective ocular delivery system of therapeutic small interfering RNA (siRNA) in corneal neovascularization therapy. The major hurdle present in siRNA-based corneal neovascularization (CNV) therapy is severe cytotoxicity caused by repetitive drug treatment. A reducible branched polyethylenimine (rBPEI)-based nanoparticle (NP) system is utilized as a new siRNA carrier as a hope for CNV therapy. The thiolated BPEI is readily self-crosslinked in mild conditions to make high molecular weight rBPEI thus allowing the creation of stable siRNA/rBPEI nanoparticles (siRNA-rBPEI-NPs). In the therapeutic region, the rBPEI polymeric matrix is effectively degraded into nontoxic LMW BPEI inside the reductive cytosol causing the rapid release of the encapsulated siRNA into the cytosol to carry out its function. The fluorescent-labeled siRNA-rBPEI-NPs can release siRNA into the entire corneal region after subconjuctival injection into the eye of Sprague Dawley rats thus confirming the proof of concept of this system.

Original languageEnglish
JournalMacromolecular Bioscience
DOIs
Publication statusAccepted/In press - 2016
Externally publishedYes

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Keywords

  • Corneal neovascularization
  • Nanoparticles
  • Ocular delivery
  • Reducible polyethylenimine
  • SiRNA

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Han, H., Son, S., Son, S., Kim, N., Yhee, J. Y., Lee, J. H., Choi, J. S., Joo, C. K., Lee, H., Lee, D., Kim, W. J., Kim, S. H., Kwon, I. C., Kim, H., & Kim, K. M. (Accepted/In press). Reducible Polyethylenimine Nanoparticles for Efficient siRNA Delivery in Corneal Neovascularization Therapy. Macromolecular Bioscience. https://doi.org/10.1002/mabi.201600051