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Intracameral Delivery of Layer-by-Layer Coated siRNA Nanoparticles for Glaucoma Therapy.

Publication ,  Journal Article
Dillinger, AE; Guter, M; Froemel, F; Weber, GR; Perkumas, K; Stamer, WD; Ohlmann, A; Fuchshofer, R; Breunig, M
Published in: Small
December 2018

Glaucoma is the second leading cause of blindness worldwide, often associated with elevated intraocular pressure. Connective tissue growth factor (CTGF) is a mediator of pathological effects in the trabecular meshwork (TM) and Schlemm's canal (SC). A novel, causative therapeutic concept which involves the intracameral delivery of small interfering RNA against CTGF is proposed. Layer-by-layer coated nanoparticles of 200-260 nm with a final layer of hyaluronan (HA) are developed. The HA-coating should provide the nanoparticles sufficient mobility in the extracellular matrix and allow for binding to TM and SC cells via CD44. By screening primary TM and SC cells in vitro, in vivo, and ex vivo, the validity of the concept is confirmed. CD44 expression is elevated in glaucomatous versus healthy cells by about two- to sixfold. CD44 is significantly involved in the cellular uptake of HA-coated nanoparticles. Ex vivo organ culture of porcine, murine, and human eyes demonstrates up to threefold higher accumulation of HA compared to control nanoparticles and much better penetration into the target tissue. Gene silencing in primary human TM cells results in a significant reduction of CTGF expression. Thus, HA-coated nanoparticles combined with RNA interference may provide a potential strategy for glaucoma therapy.

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Published In

Small

DOI

EISSN

1613-6829

Publication Date

December 2018

Volume

14

Issue

50

Start / End Page

e1803239

Location

Germany

Related Subject Headings

  • Trabecular Meshwork
  • Swine
  • RNA, Small Interfering
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice
  • Hyaluronic Acid
  • Hyaluronan Receptors
  • Humans
  • Glaucoma
 

Citation

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Dillinger, A. E., Guter, M., Froemel, F., Weber, G. R., Perkumas, K., Stamer, W. D., … Breunig, M. (2018). Intracameral Delivery of Layer-by-Layer Coated siRNA Nanoparticles for Glaucoma Therapy. Small, 14(50), e1803239. https://doi.org/10.1002/smll.201803239
Dillinger, Andrea E., Michaela Guter, Franziska Froemel, Gregor R. Weber, Kristin Perkumas, W Daniel Stamer, Andreas Ohlmann, Rudolf Fuchshofer, and Miriam Breunig. “Intracameral Delivery of Layer-by-Layer Coated siRNA Nanoparticles for Glaucoma Therapy.Small 14, no. 50 (December 2018): e1803239. https://doi.org/10.1002/smll.201803239.
Dillinger AE, Guter M, Froemel F, Weber GR, Perkumas K, Stamer WD, et al. Intracameral Delivery of Layer-by-Layer Coated siRNA Nanoparticles for Glaucoma Therapy. Small. 2018 Dec;14(50):e1803239.
Dillinger, Andrea E., et al. “Intracameral Delivery of Layer-by-Layer Coated siRNA Nanoparticles for Glaucoma Therapy.Small, vol. 14, no. 50, Dec. 2018, p. e1803239. Pubmed, doi:10.1002/smll.201803239.
Dillinger AE, Guter M, Froemel F, Weber GR, Perkumas K, Stamer WD, Ohlmann A, Fuchshofer R, Breunig M. Intracameral Delivery of Layer-by-Layer Coated siRNA Nanoparticles for Glaucoma Therapy. Small. 2018 Dec;14(50):e1803239.
Journal cover image

Published In

Small

DOI

EISSN

1613-6829

Publication Date

December 2018

Volume

14

Issue

50

Start / End Page

e1803239

Location

Germany

Related Subject Headings

  • Trabecular Meshwork
  • Swine
  • RNA, Small Interfering
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice
  • Hyaluronic Acid
  • Hyaluronan Receptors
  • Humans
  • Glaucoma