Nanoparticle-Mediated Delivery of Neuroprotective Substances for the Treatment of Diabetic Retinopathy

Diabetic retinopathy (DR) is a major complication of diabetes, characterized by extensive vascular pathology leading to vision loss. Neuronal suffering and death are also present in the diabetic retina as a result of different molecular mechanisms that are compromised or modified in response to high glucose and that mainly include excitotoxicity, advanced glycation, inflammation and oxidative stress. Recent data indicate that the vascular changes may be secondary to damage of retinal neurons and that neurodegeneration is likely to play a primary role in the development of DR. Therefore, strategies based on neuroprotection may be exploited to treat DR. However, there are important limitations related to possible systemic side effects of neuroprotective substances and to drug bioavailability in the retina such as, for instance, the amount of drug reaching the retina, the need of keeping to a minimum the number of administrations (especially, for example, in the case of intraocular injections) and the need of assuring a long-lasting, graded intraocular drug delivery. In recent years, a variety of investigations have been aimed at the exploitation of approaches of nanomedicine to enhance the pharmacokinetics and pharmacodynamic activity of intraocularly delivered drugs. We propose that nanoparticles functionalized with neuroprotective substances may be used to protect the diabetic retina, thus causing an impact in the design of future pharmacologic treatments for DR, and illustrate some preliminary results that we have obtained about the feasibility of delivering magnetic nanoparticles functionalized with a neuroprotectant to mouse eyes through intraocular injections.