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, Kwangmeyung Kim

Research output: Contribution to journalArticle

12 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. (Figure presented.).

Original languageEnglish
Pages (from-to)1583-1597
Number of pages15
JournalMacromolecular Bioscience
Volume16
Issue number11
DOIs
Publication statusPublished - 2016 Nov 1

Keywords

  • corneal neovascularization
  • nanoparticles
  • ocular delivery
  • reducible polyethylenimine
  • siRNA

ASJC Scopus subject areas

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

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  • 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. (2016). Reducible Polyethylenimine Nanoparticles for Efficient siRNA Delivery in Corneal Neovascularization Therapy. Macromolecular Bioscience, 16(11), 1583-1597. https://doi.org/10.1002/mabi.201600051