Intracameral Delivery of Layer ‐by‐Layer Coated siRNA Nanoparticles for Glaucoma Therapy

Nanoparticles loaded with siRNA against connective tissue growth factor (CTGF) and coated with a final layer of hyaluronan (HA) are proposed as a novel and causative approach for glaucoma treatment. HA ‐coated nanoparticles deeply penetrate into the outflow region of porcine, murine, and human eyes ex vivo and have the capability of silencing CTGF in cultures of human trabecular meshwork cells. AbstractGlaucoma 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 de monstrates up to threefold higher accumulation of HA compared to control nanoparticles and much better pe...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research