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Miscellaneous (28)

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Abstract #71633 Published in IGR 18-3

Six month delivery of gdnf from plga/vitamin e biodegradable microspheres after intravitreal injection in rabbits

García-Caballero C; Prieto-Calvo E; Checa-Casalengua P; García-Martín E; Polo-Llorens V; García-Feijoo J; Molina-Martínez IT; Bravo-Osuna I; Herrero-Vanrell R
European Journal of Pharmaceutical Sciences 2017; 103: 19-26

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Local long-term delivery of glial cell line derived neurotrophic factor (GDNF) from vitamin E/poly-lactic-co-glycolic acid microspheres (MSs) protects retinal ganglion cells in an animal model of glaucoma for up to 11weeks. However, the pharmacokinetics of GDNF after intravitreal injection of MSs is not known. We evaluated the GDNF levels after a single intravitreal injection of GDNF/VitE MSs. Biodegradable MSs were prepared by the solid-oil-in-water emulsion-solvent evaporation technique and characterized. Rabbits received a single intravitreal injection (50μL) of GDNF/VitE MSs (4%w/v; 24 right eyes; 74.85ng GDNF), blank MSs (4%w/v; 24 left eyes), and balanced salt solution (4 eyes). Two controls eyes received no injections. At 24h, 1, 4, 6, 8, 12, 18, and 24weeks after injection, the eyes were enucleated, and the intravitreal GDNF levels were quantified. Pharmacokinetic data were analysed according to non-compartmental model. Intraocular GDNF levels of 717.1±145.1pg/mL were observed at 24h for GDNF-loaded MSs, followed by a plateau (745.3±25.5pg/mL) until day 28. After that, a second plateau (17.4±3.7pg/mL) occurred from 8 to 24weeks post-injection, significantly higher than the basal levels. Eyes injected with GDNF/vitE and Blank-MSs did not show any abnormalities during the six-months follow up after administration. The single injection of GDNF/VitE MSs provided a sustained controlled release of the neurotrophic factor in a controlled fashion for up to six months.

Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain.

Full article

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Classification:

11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
11.8 Neuroprotection (Part of: 11 Medical treatment)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)

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