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A. Behrens, Y. A. Khan, S. K. Lai, R. T. Kashiwabuchi, W. Tattiyakul, J. Hanes, P. J. McDonnell, III; Sustained Intrastromal Drug Delivery With Micro- and Nanoparticles - A Potential Method for Treating Chronic Keratitis and Corneal Graft Rejection. Invest. Ophthalmol. Vis. Sci. 2010;51(13):442.
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Many cases of amoebic/fungal keratitis and corneal graft rejection remain refractory to topical therapy. Intrastromal (IS) injection of medications has been introduced as alternative, but efficacy remains limited due to accelerated drug clearance. The purpose of this study was to analyze the retention times of IS micro- and nanoparticles, to evaluate their use for sustained delivery of antimicrobial or immunosuppressant agents to the cornea.
New Zealand white rabbits were used in the study and divided in three groups. After obtaining baseline fluorescence images, a 3×3 mm IS pocket was dissected in one cornea of each rabbit. Control group (CG) received 10 µL of saline into the IS pocket; microparticle group (MG) received 10 µL of 1 µm particles into the pocket; and nanoparticle group (NG) received 10 µL of 200 nm particles into the pocket. The retention time of the particles was assessed by in vivo fluorescence. Images were obtained at 0 min, 1 h, 6 h, every 24 h for 1 week and every 48 h for 14 days. The initial fluorescence value for each eye was used to calculate the clearance of particles from the corneal stroma.
Overall, there was no significant difference between the clearance profiles of the micro- vs. nanoparticles at any time point evaluated (P<0.05). At 1h, there was a clearance of 21% (MG) and 23% (NG); at 24 h, 52% (MG) and 41% (NG); and at 14 days, 79% (MG) and 73% (NG). The CG had no detectable fluorescence at any time point.
IS micro- and nanoparticles seem to persist in the cornea for over two weeks in this in vivo rabbit animal model. The possibility of loading these particles with medications offers a method for providing long-term drug delivery to the cornea, which is paramount in the management of most keratitis and graft rejection.
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