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

Adi Tzameret, Hadas Ketter-Katz, Victoria Edelshtain, Ifat Sher, Enav Corem-Salkmon, Itay Levy, David Last, David Guez, Yael Mardor, Shlomo Margel, Ygal Rotenstrich

Research output: Contribution to journalArticle

Abstract

Background: Retinal 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. Results: Twenty-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. Conclusions: MRI 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.

Original languageEnglish (US)
Article number3
JournalJournal of nanobiotechnology
Volume17
Issue number1
DOIs
StatePublished - Jan 10 2019

Fingerprint

Posterior Eye Segment
Retinal Degeneration
Magnetic resonance
Iron oxides
Serum Albumin
Nanoparticles
Rats
Magnetic Resonance Imaging
Imaging techniques
Animals
Injections
Histology
ferric oxide
Retinal Diseases
Choroid
Pathology
Therapeutics
Drug delivery
Half-Life
Retina

Keywords

  • Iron oxide nanoparticles
  • RCS rats
  • Retinal degeneration
  • Suprachoroidal injection

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology
  • Pharmaceutical Science

Cite this

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. / Tzameret, Adi; Ketter-Katz, Hadas; Edelshtain, Victoria; Sher, Ifat; Corem-Salkmon, Enav; Levy, Itay; Last, David; Guez, David; Mardor, Yael; Margel, Shlomo; Rotenstrich, Ygal.

In: Journal of nanobiotechnology, Vol. 17, No. 1, 3, 10.01.2019.

Research output: Contribution to journalArticle

Tzameret, Adi ; Ketter-Katz, Hadas ; Edelshtain, Victoria ; Sher, Ifat ; Corem-Salkmon, Enav ; Levy, Itay ; Last, David ; Guez, David ; Mardor, Yael ; Margel, Shlomo ; Rotenstrich, Ygal. / 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. In: Journal of nanobiotechnology. 2019 ; Vol. 17, No. 1.
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abstract = "Background: Retinal 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. Results: Twenty-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. Conclusions: MRI 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.",
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AU - Sher, Ifat

AU - Corem-Salkmon, Enav

AU - Levy, Itay

AU - Last, David

AU - Guez, David

AU - Mardor, Yael

AU - Margel, Shlomo

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