Intravitreal delivery of corticosteroid nanoparticles

Age-related macular degeneration and diabetic retinopathy occurring in the posterior region of the eye are the leading causes of blindness among the elderly. Treatments for these diseases currently include laser photocoagulation and photodynamic therapy. However, aforementioned methods help in eliminating only the existing neovascularization but do not treat the cause of the disease resulting in reoccurrence. Recently corticosteroids are being used to treat posterior ocular diseases due to their angiostatic and antipermeable properties. The rationale for the use of corticosteroids for these conditions is their ability to inhibit growth factors like vascular endothelial growth factor (VEGF). Drug delivery to the posterior segment of the eye is very challenging. One of the major concerns with intravitreal delivery is that repeated injections are disagreeable and lead to further complications. Sustained release systems including microspheres, liposomes and other implant devices offer an excellent alternative to multiple intravitreous injections.;The development of drug delivery systems is becoming important in the treatment of vitreoretinal diseases not only to facilitate drug efficacy but also to attenuate the side effects. These systems can enhance the permeation of the drug, help in controlled release of the drug. Biodegradable poly(lactide-co-glycolide) corticosteroid nanoparticles were prepared and characterized for size, drug encapsulation and in vitro drug release. In order to obtain nanoparticles of desired size and drug loading, it is important to understand the effect of various formulation variables on particle characterization. Here we studied the effect of polymer, drug and surfactant concentration. Increasing the polymer concentration increased the size of the particles. While increase in surfactant concentration decreased the size of the particles and also drug loading.;Cell culture studies were conducted to understand the effect of the corticosteroid nanoparticles on cell toxicity, cell uptake and VEGF secretion. Decrease in toxicity was seen with nanoparticles and use of soft steroid. The uptake of the particles was time and concentration dependent.;Finally, we investigated the efficacy of intravitreal corticosteroid loaded nanoparticles on experimental choroidal neovascularization in a laser-induced mice model. The corticosteroid nanoparticles showed a significant decrease in neovascularization area compared to the control indicating that corticosteroid-loaded polymer nanoparticles can inhibit the development of experimental choroidal neovascularization.