Magnetic nanoparticles: a strategy to target the choroidal layer in the posterior segment of the eye

Abstract

Despite the higher rate of blindness due to population aging, minimally invasive and selective drug delivery to the eye still remains an open challenge, especially in the posterior segment. The retina, the retinal pigment epithelium (RPE) and the choroid are posterior segment cell layers, which may be affected by several diseases. In particular, damages to the choroid are associated with poor prognosis in the most severe pathologies. A drug delivery approach, able to target the choroid, is still missing. Recently, we demonstrated that intravitreally injected magnetic nanoparticles (MNP) are able to rapidly and persistently localise within the RPE in an autonomous manner. In this work we functionalised the MNP surface with the vascular endothelial growth factor, a bioactive molecule capable of transcytosis from the RPE towards more posterior layers. Such functionalisation successfully addressed the MNPs to the choroid, while MNP functionalised with a control polypeptide (poly-L-lysine) showed the same localisation pattern of the naked MNP particles. These data suggest that the combination of MNP with different bioactive molecules could represent a powerful strategy for cell-specific targeting of the eye posterior segment.

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress

“…Briefly, the MNP:protein suspension was incubated at 4 °C for 2 h with stirring. For BDNF and BSA, particles were covalently functionalized via EDC chemistry, according to a protocol that we optimized in previous studies with other proteins [ 22 , 25 , 26 ]. Briefly, particles were centrifuged (18,000 g ) and resuspended in 4% EDC (Sigma) water solution.…”

“…In previous studies, we demonstrated that magnetic nanoparticles (MNPs) could be used to bypass the limitations related to the IVT injection of free proteins [ 21 , 22 ]. MNPs are largely used in biomedicine.…”

“…We found that IVT-injected MNPs autonomously localise themselves in the retina where they persist for at least 3 weeks [ 21 , 22 ]. In principle, MNP-mediated drug delivery could provide a therapeutically effective concentration of the carried molecule for weeks in the right location, thereby preventing side effects in other tissues.…”

Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy

“…According to this model, MNPs diffusing into the retinal cell layers would be forced to move along narrow intercellular spaces, which would cause their clusterization. Then these small MNP aggregates would reach the RPE having a micrometric dimension ideal for promoting engulfment by RPE cells (Kimura et al, 1994;Giannaccini et al, 2017b). In addition, some MNP-OCT were observed in intimate contact with the surface of some cells in the INL.…”

“…Different types of nanoparticles have been tested as carriers for the intraocular delivery of drugs inhibiting choroidal or intraretinal neovascularization, thus indicating therapeutic potential for age-related macular degeneration (Park et al, 2009;Liu et al, 2011;Cai and McGinnis, 2016), while nanoparticlebased approaches for the treatment of DR have also been investigated (Fangueiro et al, 2015). Among nanoparticles, magnetic nanoparticles (MNPs) may represent a promising perspective for intraocular drug delivery (Giannaccini et al, 2017b). Indeed, intraocularly injected MNPs have been shown to enter the retina rapidly and persistently localize within the retinal pigment epithelium (RPE) in Xenopus and zebrafish without inducing any tissue damage (Giannaccini et al, 2014).…”