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Nobuhiro Nagai, Hirokazu Kaji, Zhaleh Kashkouli Nezhad, Kaori Sampei, Satoru Iwata, Matsuhiko Nishizawa, Yukihiko Mashima, Toshiaki Abe; Controlled Transscleral Dual-drug Delivery by a Polymeric Device Reduces Light-induced Retinal Damage. Invest. Ophthalmol. Vis. Sci. 2014;55(13):446.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the protective effects of a transscleral dual-drug delivery device that can release unoprostone isopropyl (UNO) and edaravone (EDV) at independently controlled release rates against light-induced retinal damage in rats.
The device consists of a reservoir, controlled-release cover, and drug formulations, which were made of photopolymeized poly(ethyleneglycol) dimethacrylate that partially contains tri(ethyleneglycol) dimethacrylate. These parts were fabricated via a microfabrication technique that used an AutoCAD design. UNO, a prostanoid for antiglaucoma eyedrops marketed in Japan, and EDV, a potent free radical scavenger, were loaded in the device. High-performance liquid chromatography was used to evaluate the release amount of UNO and EDV. After the devices were placed onto the sclera of eyes in rats for 1 week, the rats were exposed to 8000 lux of white fluorescent light for 24 h, then flash electroretinograms were recorded. Histological examinations were perfomred to evaluate the thickness of the outer nuclear layer and the number of apoptotic cells.
UNO and EDV were simultaneously released with zero-ordered kinetics from the device. Trannsscleral co-administration of EDV and UNO by the device reduced loss of retinal function assessed by electroretinograms compared to single administration. The device also precluded the reductions of retinal thickness and the number of apoptotic cells after light exposure.
Co-delivery of EDV and UNO by our device attenuates light-induced retinal damage morphologically and functionally. Controlled dual-drug delivery using our device can protect retinal function from light damage by a less invasive transscleral administration.
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