Lipid-DNA Nanoparticles as Drug-Delivery Vehicles for the Treatment of Retinal Diseases

Abstract

Retinal eye diseases are the leading cause of blindness in the Western world. Up to date, the only efficient treatment for many retinal diseases consists of invasive intravitreal injections of highly concentrated drugs. Despite the fact that these injections are unpleasant for the patients, they potentially cause serious side effects, e.g., infections, bleeding within the eye or retinal detachment, especially when performed on a monthly basis, thus decreasing the injection frequency and lowering the desired drug dose. Therefore, a sustained released at the region of interest with a sustained release is desired. Recently, novel lipid-DNA nanoparticles (NPs) were shown to be an efficient drug delivery platform to the anterior segment of the eye. In this study, we investigated the distribution and tropism of the NPs when applied intravitreally, as a potential medication carrier to the posterior part of the eye. This technology is perfectly suited for the delivery of low molecular weight drugs to the back of the eye, which so far is greatly hindered by fast diffusion rates of the free drugs in the vitreous body and their intrinsically low retainability in ocular tissue. Excellent biodistribution, adherence and presence for up to five days was found for the different tested nanoparticles ex vivo and in vivo. In conclusion, our lipid-DNA based nanocarrier system was able to reach the retina within minutes and penetrate the retina providing potentially safe and long-term carrier systems for small molecules or nucleotide-based therapies.

Advancements in Nanogels for Enhanced Ocular Drug Delivery: Cutting-Edge Strategies to Overcome Eye Barriers

“…The experiment confirmed improved residence time in porcine and human corneal tissue compared to the original drug, highlighting the potential to increase the in vivo efficiency of these drug delivery systems. Subsequent studies conducted by other research groups have supported the potential of DNA nanocarriers for intraocular drug delivery [ 232 , 233 , 235 ]. In an in vivo experiment reported by one research group, nanoparticles were injected into the eye tissue of rats and it was found that although the drug appeared diffused when compared to injections into the vitreous cavity, adhesion to retinal tissue was still achieved up to 5 days [ 232 ].…”

“…Subsequent studies conducted by other research groups have supported the potential of DNA nanocarriers for intraocular drug delivery [ 232 , 233 , 235 ]. In an in vivo experiment reported by one research group, nanoparticles were injected into the eye tissue of rats and it was found that although the drug appeared diffused when compared to injections into the vitreous cavity, adhesion to retinal tissue was still achieved up to 5 days [ 232 ]. As demonstrated in another study, the nanoparticles effectively lowered intraocular pressure compared to the native drug due to the increased adhesion of NPs to the corneal surface for up to 4 h in vitro and up to 1 h in vivo (in pig eyes and rats) [ 233 ].…”