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/choroid 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.

Highlights

  • Disorders of the retina and retinal pigmented epithelium (RPE)/choroid tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood.The most prevalent posterior segment diseases include age related macular degeneration (AMD), diabetic retinopathy, and retinal degenerative disorders such as retinitis pigmentosa

  • We have investigated the ability of magnetic nanoparticles (MNPs) to target RPE by IVT injection, using wild type Xenopus laevis as model system

  • These results indicate that the MNPs progressively migrate at RPE from the vitreous chamber (Figure 3b–d) and that the migration process is completed within 24 h (Figure 3e,f)

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Summary

Introduction

Disorders of the retina and retinal pigmented epithelium (RPE)/choroid tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood. Pharma AG, Berlin, Germany, MRI contrast agent for diagnosis of liver metastases and colon cancer), Feraheme® (Amag Pharmaceutical Inc., Cambridge, USA, indicated for the treatment of iron deficiency anemia in adult patients with chronic kidney disease), etc Another challenging application of MNPs is magnetic hyperthermia [19]. A remarkable similarity in the molecular signaling processes, cellular structure, anatomy, and physiology of eye has been observed among Xenopus and other high-order vertebrates, including humans [24] Their relatively large size (from 1–1.2 mm (zygote) to 1 cm (120 h post fertilization)) enables an easy manipulation and IVT microinjection. Biodistribution and localization studies were performed and the effect of the particle size and charge was assessed

MNP Biodistribution
Particles Injected Intraocularly Localize behind the Neural Retina
MNP Localization Is not Driven by Superficial Charge and Size
Nanoparticles
Embryo Preparation
Embryo Microinjections
Histochemical Analysis
Iron Content Assay
Conclusions
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