Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits



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García-Caballero, Cristina and Prieto-Calvo, Esther and Checa-Casalengua, Patricia and García-Martín, Elena and Polo-Llorens, Vicente and García-Feijoo, Julián and Molina-Martínez, Irene Teresa and Bravo-Osuna, Irene and Herrero-Vanrell, Rocío (2017) Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits. European Journal of Pharmaceutical Sciences, 103 . pp. 19-26. ISSN 0928-0987

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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 11 weeks. 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 (50 μL) of GDNF/VitE MSs (4%w/v; 24 right eyes; 74.85 ng GDNF), blank MSs (4%w/v; 24 left eyes), and balanced salt solution (4 eyes). Two controls eyes received no injections. At 24 hours, 1, 4, 6, 8, 12, 18, and 24 weeks 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 ± 145.1 pg/mL were observed at 24 hours for GDNF-loaded MSs, followed by a plateau (745.3 ± 25.5 pg/mL) until day 28. After that, a second plateau (17.4 ± 3.7 pg/mL) occurred from 8 to 24 weeks postinjection, 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.

Item Type:Article
Uncontrolled Keywords:Poly (lactic-co-glycolic acid) microspheres, Protein delivery, Vitamin E, Glial cell line-derived neurotrophic factor (GDNF), Pharmacokinetics, Intravitreal injection.
Subjects:Medical sciences > Pharmacy
Medical sciences > Pharmacy > Pharmaceutical technology
ID Code:51764
Deposited On:08 Mar 2019 13:00
Last Modified:11 Mar 2019 08:39

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