John Garner

Fluorescent PLGA-rhodamine from PolySciTech used in development of siRNA nanoparticle therapy against glaucoma

Blog Post created by John Garner on Oct 25, 2018

Dillinger, 2018 intracameral delivery.PNG

Glaucoma is a progressive disease which damages the eye’s optic nerves eventually leading to blindness if left untreated. The overgrowth of connective tissue (e.g. non-nerve based tissue for mechanical strength) is affiliated with the progression of this disease and silencing the genes associated with this may delay glaucoma’s progression. Recently, researchers at University Regensburg (Germany) used PLGA-rhodamine (PolyVivo AV011) from PolySciTech (www.polyscitech.com) as part of developing silencing RNA delivery nanoparticles as a potential therapy for glaucoma. This research holds promise to reduce blindness associated with this disease. Read more: Andrea E. Dillinger, Michaela Guter, Franziska Froemel, Gregor R. Weber, Kristin Perkumas, W. Daniel Stamer, Andreas Ohlmann, Rudolf Fuchshofer, Miriam Breunig   “Intracameral Delivery of Layer‐by‐Layer Coated siRNA Nanoparticles for Glaucoma Therapy” Small 2018, 1803239. https://doi.org/10.1002/smll.201803239

 

  “Abstract: 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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