In vivo evaluation of a biodegradable donut-shaped minitablet for prolonged posterior segment drug delivery in the rabbit eye model
Journal of Pharmaceutical Sciences
University of the Witwatersrand, Department of Pharmacy and Pharmacology, Parktown 2193, Johannesburg, Gauteng, South Africa; University of the Witwatersrand, Division of Neurosciences, Department of Ophthalmology, Parktown 2193, Johannesburg, Gauteng, South Africa; University of the Witwatersrand, Department of Physiology, Brian Function Research Group and Central Animal Services, Parktown 2193, Johannesburg, Gauteng, South Africa; University of the Witwatersrand, Department of Anatomical Pathology, Parktown 2193, Johannesburg, Gauteng, South Africa
This study focused on the in vivo evaluation of a biodegradable ganciclovir-loaded donut-shaped minitablet (DSMT) for controlled drug delivery in the New Zealand white albino rabbit eye model. Specialized tablet tooling was used to manufacture a poly(lactic-co-glycolic acid) DSMT device that was implanted into 18 rabbits through the pars plana/peripheral retina of the right eyes of each rabbit. The left eyes were used as controls. Possible adverse effects on ocular tissues were assessed by histomorphology, slit-lamp biomicroscopy, intraocular pressure (IOP) measurements, and indirect ophthalmoscopy. The ex vivo microenvironmental vitreous pH was also monitored. Rabbits were euthanized at predetermined intervals and the residual devices, vitreous humor, and ocular tissue were retrieved and stored appropriately until further analysis. The DSMT was well tolerated up to 72 days and was still visible in the superotemporal quadrant of the eye. The mean IOP range (6-8 mmHg; N = 18) and changes in vitreous pH (7.25 ± 0.01; N = 3) correlated with baseline measurements. The DSMT displayed constant ganciclovir release at a rate of 2.02 μg/h maintained within the 50% effective dose for human cytomegalovirus retinitis (N = 3). The design simplicity and application of the biodegradable DSMT device may provide a superior alternative for prolonged rate-controlled intraocular drug delivery. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association.
ganciclovir; polyglactin; resomer; adverse outcome; animal experiment; animal tissue; area under the curve; article; biodegradation; ciliary disk; controlled study; donut shaped minitablet; drug bioavailability; drug blood level; drug delivery system; drug elimination; drug isolation; drug release; ex vivo study; histology; in vivo study; intraocular pressure; male; nonhuman; ophthalmoscopy; pH; rabbit; retina; slit lamp; toxicity testing; vitreous body; Absorbable Implants; Animals; Antiviral Agents; Delayed-Action Preparations; Drug Delivery Systems; Equipment Design; Ganciclovir; Hydrogen-Ion Concentration; Lactic Acid; Male; Polyglycolic Acid; Posterior Eye Segment; Rabbits