May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Particle Surface Functionalization for Enhanced Nanoparticle Delivery to the Anterior and the Posterior Segments of the Eye
Author Affiliations & Notes
  • S. Raghava
    Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, Nebraska
  • S. Sundaram
    Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, Nebraska
  • E. R. Escobar
    Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, Nebraska
  • H. F. Edelhauser
    Emory Eye Center, Atlanta, Georgia
  • U. B. Kompella
    Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, Nebraska
  • Footnotes
    Commercial Relationships S. Raghava, None; S. Sundaram, None; E.R. Escobar, None; H.F. Edelhauser, None; U.B. Kompella, None.
  • Footnotes
    Support NIH Grant EY017045
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5798. doi:
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    • Get Citation

      S. Raghava, S. Sundaram, E. R. Escobar, H. F. Edelhauser, U. B. Kompella; Particle Surface Functionalization for Enhanced Nanoparticle Delivery to the Anterior and the Posterior Segments of the Eye. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5798.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: To enhance nanoparticle delivery to cornea and conjunctiva of the anterior segment and retinal pigment epithelium of the posterior segment of the eye.

Methods:: Anionic fluospheres < 100 nm in diameter (NP) were conjugated to deslorelin (deslorelin-NP), a nonapeptide luteinizing hormone releasing hormone (LHRH) agonist, and transferrin (transferrin-NP). Nanoparticle drop was topically administered to a novel ex vivo bovine eye model and the nanoparticles in corneal epithelium, stroma, and endothelium were quantified at 5 and 60 min. The uptake of nanoparticles into cultured human retinal epithelial cells (ARPE-19) was studied by exposing nanoparticle suspension to confluent cells and quantifying the uptake at 3 h using spectrofluorometry. Further, the transport of nanoparticles over 4 h was studied using excised bovine cornea and conjunctiva mounted in Ussing chambers. Confocal microscopy was employed to visualize nanoparticles within various layers of cornea, conjunctiva, and ARPE-19 cells. Real time PCR and western blot were carried out to determine the expression of LHRH and transferrin receptors in cornea and conjunctiva.

Results:: Deslorelin and transferrin conjugation enhanced corneal epithelial uptake of nanoparticles by 3- and 4.5 fold at 5 min and by 4.5- and 3.8 fold at 60 min. The total corneal uptake in 5 min was approximately 2.4, 9, and 16% with plain, deslorelin functionalized, and transferrin functionalized particles, respectively. In all groups, the nanoparticle uptake per unit tissue weight was in the order: corneal epithelium > stroma > endothelium with the levels in aqueous humor being undetectable even at 1 h. Deslorelin and transferrin conjugation significantly enhanced the 4 h uptake and transport of nanoparticles across excised bovine cornea as well as conjunctiva. The retinal pigment epithelial cell uptake of deslorelin-NP and transferrin-NP was significantly greater than unconjugated NP. The uptake enhancement was reduced in the presence of free ligand and at 4 °C. Real time PCR and western blot indicated the expression of receptors for LHRH and transferrin in bovine corneal epithelium and conjunctiva.

Conclusions:: Surface functionalized nanoparticles in an eye drop allow as much as 16% dose delivery to the cornea within 5 min. This approach is useful for cells of the posterior segment as well. The delivery enhancement involves the interaction of ligands on nanoparticles with cell surface receptors.

Keywords: anterior segment • retinal pigment epithelium • drug toxicity/drug effects 
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