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Macromol Biosci. 2016 Nov;16(11):1583-1597. doi: 10.1002/mabi.201600051. Epub 2016 Aug 9.

Reducible Polyethylenimine Nanoparticles for Efficient siRNA Delivery in Corneal Neovascularization Therapy.

Author information

1
Center for Theragnosis, Biomedical Research Institute Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul, 136-791, South Korea.
2
Department of Chemical and Biomolecular Engineering, Sogang University, Shinsu-dong, Mapo-gu, Seoul, 121-742, South Korea.
3
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul, 137-040, South Korea.
4
Center for Self-Assembly and Complexity, Institute for Basic Science (IBS), Pohang, 790-784, South Korea.
5
Department of Chemistry Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, South Korea.

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.

KEYWORDS:

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

PMID:
27503770
DOI:
10.1002/mabi.201600051
[Indexed for MEDLINE]

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