The Application of Methylprednisolone Nanoscale Zirconium-Porphyrin Metal-Organic Framework (MPS-NPMOF) in the Treatment of Photoreceptor Degeneration

Int J Nanomedicine. 2019 Dec 10:14:9763-9776. doi: 10.2147/IJN.S225992. eCollection 2019.

Abstract

Background: Photoreceptor degeneration is one of the most refractory oculopathy in the world, leading to vision loss in severe cases. Methyprednisolone is one of the most commonly prescribed medications for the treatment of retinal degenerative diseases, either by oral administration or repeated intraocular injections. However, the efficacy was unsatisfactory due to its systemic or local side effects and short retention time within the retina.

Methods: Nanoscale zirconium-porphyrin metal-organic framework (NPMOF) was synthesized and characterized. The biotoxicity and imaging capability of NPMOF were evaluated using zebrafish embryos and larvae. NPMOF was then used as a skeleton and loaded with methylprednisolone (MPS) to prepare a novel kind of nanoparticle, MPS-NPMOF. Photoreceptor degeneration was induced by high-intensity light exposure in adult zebrafish. MPS-NPMOF was delivered to the injured retina by intraocular injection. The photoreceptor regeneration and its underlying mechanism were explored by immunohistochemistry, quantitative real-time polymerase chain reaction and behavioral test.

Results: NPMOF not only had low biotoxicity but also emitted bright fluorescence. Following a single MPS-NPMOF intraocular injection, the injured retina exhibited the faster photoreceptor regeneration with better visual function by promoting the cell proliferation.

Conclusion: NPMOF is an ideal carrier and could be applied in tracking and delivering medications. By intraocular injection, the novel drug delivery system, MPS-NPMOF, accomplishes the sustained release of drug and plays a therapeutic role in photoreceptor degeneration.

Keywords: degeneration; drug delivery; methylprednisolone; nanoscale zirconium-porphyrin metal-organic framework; photoreceptor.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • Embryo, Nonmammalian / drug effects
  • Fluorescence
  • Injections, Intraocular
  • Metal-Organic Frameworks / administration & dosage
  • Metal-Organic Frameworks / chemistry*
  • Metal-Organic Frameworks / pharmacology
  • Methylprednisolone / administration & dosage*
  • Methylprednisolone / pharmacology
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry
  • Photoreceptor Cells, Vertebrate / metabolism
  • Porphyrins / chemistry*
  • Retina / drug effects
  • Retina / injuries
  • Retinal Degeneration / drug therapy*
  • Retinal Degeneration / etiology
  • Zebrafish / embryology
  • Zirconium / chemistry*

Substances

  • Metal-Organic Frameworks
  • Porphyrins
  • Zirconium
  • Methylprednisolone