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Sho Koda, Takashi Saito, Junji Kitano, Naoki Okumura, Shigeru Kinoshita, Yasuhiko Tabata, Noriko Koizumi; Controlled Release of a Rho Kinase (ROCK)-Selective Inhibitor with Polylactic Acid Microspheres. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1689.
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We previously reported that the Rho kinase (ROCK) inhibitor Y-27632 promoted the wound healing of corneal endothelial cells in a primate model. Thus, Y-27632 shows promise as a drug that can be used for the clinical treatment of corneal endothelial defects. The purpose of this present study was to design polylactic acid (PLA) microspheres that can be used for the controlled release of Y-27632 in the anterior chamber.
PLA microspheres incorporating Y-27632 (Y-27632-PLA) were prepared via a double-emulsion [(water in oil) in water] solvent evaporation method. The in vitro release test of Y-27632-PLA was performed in a phosphate-buffered solution (pH7.4) at 37°C.The amount of Y-27632 released was determined by use of high-performance liquid chromatography (HPLC). To evaluate the toxicity of PLA microspheres without Y-27632 after they were injected into the anterior chamber of rabbit eyes, slit-lamp examinations, and corneal thickness and intraocular pressure measurements were performed up to14 days after injection, followed by immunohistochemical analysis.
Y-27632 was released from PLA microspheres over 28 days. The percent of Y-27632 released was 70.0, 77.9, and 98.2% at 7, 14, and 28 days, respectively. The release pattern of Y-27632 could be changed by altering the molecular weight of the PLA that was used. In all eyes injected with the PLA microspheres, normal corneal thickness was observed, with no inflammation or elevation of intraocular pressure. The corneal endothelial cell density and the expression of functional protein were found to be normal.
The findings of this study demonstrate that PLA microspheres are promising candidates for the controlled release of Y-27632. The Y-27632-PLA is applicable as a pharmaceutical agent for the treatment of corneal endothelial dysfunction.
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