May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Subconjunctivally administered celecoxib–PLGA microparticles sustain retinal drug levels and alleviate diabetes–induced retinal oxidative stress
Author Affiliations & Notes
  • S.P. Ayalasomayajula
    Pharmaceutical Sciences,
    University of Nebraska Medical Center, Omaha, NE
  • U.B. Kompella
    Pharmaceutical Sciences,
    Ophthalmology,
    University of Nebraska Medical Center, Omaha, NE
  • Footnotes
    Commercial Relationships  S.P. Ayalasomayajula, None; U.B. Kompella, None.
  • Footnotes
    Support  DK 064172
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3957. doi:
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      S.P. Ayalasomayajula, U.B. Kompella; Subconjunctivally administered celecoxib–PLGA microparticles sustain retinal drug levels and alleviate diabetes–induced retinal oxidative stress . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3957.

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

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Abstract

Abstract: : Purpose:We have previously reported that celecoxib, a selective COX–2 inhibitor, inhibits diabetes–induced retinal VEGF expression and that retinal celecoxib delivery can be improved by several–fold following subconjunctival administration. The objective of the current study was to determine whether polymeric microparticles of celecoxib sustain retinal drug levels following subconjunctival administration and alleviate diabetes–induced oxidative stress in a streptozotocin–induced diabetic rat model. Methods:Biodegradable poly (lactide–co–glycolide) (PLGA; 85:15) microparticles of celecoxib were prepared using solvent evaporation method and characterized for their size, morphology, encapsulation efficiency, and in vitro release. The celecoxib–PLGA microparticles or solution containing 0.075 mg of celecoxib was administered subconjunctivally to one eye (ipsilateral) of Sprague Dawley rats and drug levels in the sclera, retina, vitreous, lens, and cornea of ipsilateral and contralateral eyes were determined on 1, 7, and 14 days using HPLC. The effect of subconjunctivally administered celecoxib–PLGA microparticles on oxidative stress in day 14 diabetic rat retinas was determined by measuring the retinal glutathione (reduced (GSH) and oxidized (GSSG)), malondialdehyde (MDA), and 4–hydroxynonenal (HNE) levels using spectrofluorometric and colorimetric methods. Results:Solvent evaporation method produced spherical celecoxib–PLGA microparticles with mean diameters of 3.9 ± 0.6 µm and 68.5% loading efficiency. These microparticles sustained celecoxib release during the 49–day in vitro release study. Subconjunctivally administered celecoxib–PLGA microparticles sustained retinal and other ocular tissue drug levels during the 14 day study in rats. No detectable celecoxib levels were observed in the contralateral eye. Also, celecoxib–PLGA microparticles normalized the diabetes–induced decrease in retinal GSH levels and increase in MDA and HNE levels to the control levels. Conclusions:Retinal celecoxib levels can be sustained by subconjunctivally administering celecoxib–PLGA microparticles. Sustained celecoxib delivery can inhibit diabetes–induced reduction in retinal GSH levels and elevation in MDA and HNE levels. Thus, subconjunctival administration of biodegradable polymeric microparticles of celecoxib can be potentially used to treat diabetes–induced retinal disorders.

Keywords: diabetic retinopathy • drug toxicity/drug effects • oxidation/oxidative or free radical damage 
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