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T. R. Carmichael, Y. E. Choonara, V. Pillay, M. P. Dankwerts, S. Naylor; An in vivo Investigation Into a Novel Biodegradable Polymeric Device for Intravitreal Insertion. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5637.
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© ARVO (1962-2015); The Authors (2016-present)
An in vivo investigation of a novel biodegradable doughnut-shaped minitablet (DSMT) containing ganciclovir (GCV) in a rabbit model. The in vitro study showingeffective drug release from the device has been previously published.
Specially designed punches were used to manufacture the DSMT. The highest viscosity grade of Rosomer® (RG 504) was used as it had showed the slowest release in vitro. Six New Zealand White Albino rabbits were used for the initial in vivo drug release studies. The DSMT was implanted through the pars plana/peripheral retina of the right eye and sutured with 9 0 nylon using a technique similar to that used for a Vitrasert® implant. Vitreous from the left eye was used as a control. The rabbits were euthanized on days 3, 7, 14, 28, 48 and 70 and the devices and vitreous were retrieved from enucleated eyes and stored at -70C prior to GCV concentration analysis. Analyses were performed on a Waters ACQUITY UPLCTM system (Waters, Manchester, UK) consisting of an ACQUITY UPLCTM binary solvent manager and an ACQUITY UPLCTM sample manager. The recovery of GCV spiked into placebo vitreous samples during the extraction procedure was 102.69%, indicating the valid evaluation of the drug concentration in the vitreous.
A linear standard curve was used to assess the quantity of ganciclovir released from the device at various time points.A profile was obtained by measuring the percentage of GCV released versus the initial content in the device. In contrast with the previous in vitro release profiles, the in vivo release profile displayed a reduced initial burst with 20% GCV released at day 3 followed by a steady phase of diffusional release of about 40% by 28 days, about 50% by day 48 and 69% after 70 days in the rabbit eye model.The DSMT was well tolerated in the eye. Of the six rabbits, three had small postoperative hyphaemas, visible after the surgery and for up to a week. Two had vitreous haemorrhage and one of these had a retinal detachment by two weeks. There were no infections or inflammation and no cataract formation.
The device could be produced and inserted reasonably easily and cheaply and may be developed to release other medications such as steroid or antibiotics. It was shown to release ganciclovir steadily for a period of up to 70 days by which time 69% of the drug had been released.
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