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Bernard F. Godley, Gabriela A. Kulp, Tomasz Wiraszka, Edward R. Kraft, Aristides R. Koutrouvelis; Non-invasive Delivery Of Human Insulin Into The Posterior Segment Of The Rabbit Eye Using Photokinetic Transscleral Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3238. doi: https://doi.org/.
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Intravitreal needle injection is associated with risks of retinal detachment and infection. The purpose of this study was to determine the feasibility of a novel platform photokinetic technology to deliver drugs into posterior segment of the eye in a noninvasive fashion and assess the degree of irritation from the procedure.
In vivo transscleral permeation studies were performed using New Zealand white and Dutch belted rabbits. Human insulin was formulated in a gel containing various concentrations of drug and hyaluronic acid as vehicle and was delivered using a bench built prototype consisting of a 405 nm LED pulsed at 100 cps, embedded in a silicone scleral shell. Treatment was applied for 1 hour, followed by euthanasia, enucleation of both eyes, separation of different of tissue layers and measurement of human insulin content. Eye irritation was assessed via serial slit lamp exams and quantified using modified McDonald-Shaddock system. Tissues were collected for hematoxilyn/eosin staining.
Human insulin was detected in all tissue layers in the treated eye and to a lesser extent in the contralateral eye in both pigmented and non-pigmented animals. The levels varied by tissue type; the average % of donor insulin recovered in the rabbit were 25.5 ± 3 and 30.8 ±8 respectively. There were no significant differences between the 2 groups in ocular tissue drug distribution. Human insulin was also detected in rabbit serum, up to 11±2 µU/ml.Superficial corneal epithelial defects were the most severe lesions observed and resolved spontaneously by the end of the study. Our experiment did not reveal significant differences in the irritation scores between exposed and unexposed eyes at any time points, up to 96 hours. Similarly, no morphological differences were observed in tissue sections.
Our experiments showed that human insulin can be delivered successfully to different eye tissues in a noninvasive fashion using PTD. Permeation of insulin into rabbit eye was not affected by pigmentation. Insulin delivery into the rabbit eye was accomplished without significant damage to the eye. PTD may be an alternative approach for posterior segment drug delivery which avoids the disadvantages of intravitreal needle injection.
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