Layer-by-layer coated nanoparticles for glaucoma therapy: Focusing on the transport and cellular uptake in the trabecular meshwork

ummary Primary open angle glaucoma is one of the leading causes of blindness worldwide. The major risk factor is an elevated intraocular pressure (IOP), which leads to irreversible damage of the optical nerve head. Connective tissue growth factor (CTGF) is thought to be one of the major mediators of these pathological effects. Topical eye drops are the first-line medication for controlling an abnormally high IOP, but they have a long list of drawbacks. Consequently, there is a strong need for new therapeutic concepts to prevent vision loss. We hypothesize that a reduction of CTGF would achieve a more permanent and causative effect in regulating the IOP compared to available standard treatment regimes. To follow up this goal we developed biodegradable layer-by-layer coated nanoparticles of well-defined physicochemical properties that carry therapeutic doses of small interfering RNA for CTGF silencing. The nanoparticles had a size of about 200 nm as determined by laser light scattering and a zeta potential of about – 18 mV. We tested the CTGF silencing efficacy of the nanoparticles in primary trabecular meshwork cells. In addition, we determined the diffusion of nanoparticles in collagen I as a model for the extracellular matrix (ECM) of the trabecular meshwork by fluorescence recovery after photobleaching. An important result was that hyaluronan is favorable material for nanoparticle assembly because it allows for receptor-mediated uptake of the nanoparticles into trabecular meshwork cells on the one hand, and may provide for good nanoparticle mobility in the ECM on the other hand.