One of the most challenging efforts in drug delivery is the targeting of the eye. The eye structure and barriers render this organ poorly permeable to drugs. Quite recently the entrance of nanoscience in ocular drug delivery has improved the penetration and half-life of drugs, especially in the anterior eye chamber, while targeting the posterior chamber is still an open issue. The retina and the retinal pigment epithelium tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood. In the present study, we used magnetic nanoparticles (MNPs) as a nanotool for ocular drug delivery that is capable of specific localization in the retinal pigmented epithelium (RPE) layer. We demonstrate that, following intraocular injection in Xenopus embryos, MNPs localize specifically in RPE where they are retained for several days. The specificity of the localization did not depend on particle size and surface properties of the MNPs used in this work. Moreover, through similar experiments in zebrafish, we demonstrated that the targeting of RPE by the nanoparticles is not specific for the Xenopus species. We speculate that MNPs, can diffuse in the vitreous, infiltrate among retinal neurons without cells engulfing until their reach RPE which have a strong phagocytic activity. We are testing our functionalized MNPs as delivery system of VEGF to induce neoangiogenesis in the choroidal layer (underlying the RPE) of injected embryos. This should allow fast and precise monitoring of the activity of delivered VEGF in the target site as a concept proof for different drug targeting to the RPE in a variety of retinopathies. Moreover, our MNPs can be controlled by noncontact forces and tracked by magnetic resonance imaging and they could be exploited also for magnetic hyperthermia treatments of ocular iper-proliferative diseases and for magnetic targeting of RPE in the treatment of retinal detachment.

Drug delivery to retinal pigmented epithelium via magnetic nanoparticles

M. Giannaccini
;
GIANNINI, MARIANNA;L. Dente;V. Raffa
2014

Abstract

One of the most challenging efforts in drug delivery is the targeting of the eye. The eye structure and barriers render this organ poorly permeable to drugs. Quite recently the entrance of nanoscience in ocular drug delivery has improved the penetration and half-life of drugs, especially in the anterior eye chamber, while targeting the posterior chamber is still an open issue. The retina and the retinal pigment epithelium tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood. In the present study, we used magnetic nanoparticles (MNPs) as a nanotool for ocular drug delivery that is capable of specific localization in the retinal pigmented epithelium (RPE) layer. We demonstrate that, following intraocular injection in Xenopus embryos, MNPs localize specifically in RPE where they are retained for several days. The specificity of the localization did not depend on particle size and surface properties of the MNPs used in this work. Moreover, through similar experiments in zebrafish, we demonstrated that the targeting of RPE by the nanoparticles is not specific for the Xenopus species. We speculate that MNPs, can diffuse in the vitreous, infiltrate among retinal neurons without cells engulfing until their reach RPE which have a strong phagocytic activity. We are testing our functionalized MNPs as delivery system of VEGF to induce neoangiogenesis in the choroidal layer (underlying the RPE) of injected embryos. This should allow fast and precise monitoring of the activity of delivered VEGF in the target site as a concept proof for different drug targeting to the RPE in a variety of retinopathies. Moreover, our MNPs can be controlled by noncontact forces and tracked by magnetic resonance imaging and they could be exploited also for magnetic hyperthermia treatments of ocular iper-proliferative diseases and for magnetic targeting of RPE in the treatment of retinal detachment.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/880521
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