In vivo MRI assessment of bioactive magnetic iron oxide/human serum albumin nanoparticle delivery into the posterior segment of the eye in a rat model of retinal degeneration

Abstract

BackgroundRetinal degeneration diseases affect millions of patients worldwide and lead to incurable vision loss. These diseases are caused by pathologies in the retina and underlying choroid, located in the back of the eye. One of the major challenges in the development of treatments for these blinding diseases is the safe and efficient delivery of therapeutics into the back of the eye. Previous studies demonstrated that narrow size distribution core–shell near infra-red fluorescent iron oxide (IO) nanoparticles (NPs) coated with human serum albumin (HSA, IO/HSA NPs) increase the half-life of conjugated therapeutic factors, suggesting they may be used for sustained release of therapeutics. In the present study, the in vivo tracking by MRI and the long term safety of IO/HSA NPs delivery into the suprachoroid of a rat model of retinal degeneration were assessed.ResultsTwenty-five Royal College of Surgeons (RCS) pigmented rats received suprachoroidal injection of 20-nm IO/HSA NPs into the right eye. The left eye was not injected and used as control. Animals were examined by magnetic resonance imaging (MRI), electroretinogram (ERG) and histology up to 30 weeks following injection. IO/HSA NPs were detected in the back part of the rats’ eyes up to 30 weeks following injection by MRI, and up to 6 weeks by histology. No significant differences in retinal structure and function were observed between injected and non-injected eyes. There was no significant difference in the weight of IO/HSA NP-injected animals compared to non-injected rats.ConclusionsMRI could track the nanoparticles in the posterior segment of the injected eyes demonstrating their long-term persistence, and highlighting the possible use of MRI for translational studies in animals and in future clinical studies. Suprachoroidal injection of IO/HSA NPs showed no sign of adverse effects on retinal structure and function in a rat model of retinal degeneration, suggesting that suprachoroidal delivery of IO/HSA NPs is safe and that these NPs may be used in future translational and clinical studies for extended release drug delivery at the back of the eye.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0438-y) contains supplementary material, which is available to authorized users.

Synergic Effect of Novel WS2 Carriers Holding Spherical Cobalt Ferrite @cubic Fe3O4 (WS2/s-CoFe2O4@c-Fe3O4) Nanocomposites in Magnetic Resonance Imaging and Photothermal Therapy for Ocular Treatments and Investigation of Corneal Endothelial Cell Migration

“…MRI is a strong medical imaging technique that can provide great anatomical detail. It works by interaction of protons with the tissue’s surrounding molecules [ 58 , 59 ]. To improve the resolution and specificity of MRI, the use of the effective contrast agents is important.…”

“…The maps were recognized using six-spin echo (SE) images of TE and TR. The T1 and T 2 -weighted images were analyzed using a non-linear least-square curve using pixel intensities basis (Levenberg–Marquardt fit) using MATLAB (MathWorks inc. Natick, MA, USA) [ 59 ]. The r 1 and r 2 relaxivities were calculated from the slop of 1/T 1 and 1/T 2 (i.e., reciprocal for T 1 and T 2 relaxation times) versus the nano composite’s concentrations.…”

Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives

“…Based on their results, the nanoparticles suppressed retinal degeneration [ 104 ]. By administering HSA nanoparticles via suprachoroidal injection in retinal degeneration rat model, Tzameret et al found that the structure and function of the retina were significantly different between treated eyes and control eyes [ 105 ]. Kim et al evaluated brimonidine-loaded HSA nanoparticles in optic nerve crush rat model.…”

The utility and risks of therapeutic nanotechnology in the retina

“…The lack of toxicity shown is promising for use in extended drug delivery. 38 There are no available treatments for inherited retinal degeneration. Nanoparticles are a promising novel therapeutic tool for gene delivery in these disorders.…”