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R. Herrero-Vanrell, P. Checa-Casalengua, I. T. Molina-Martínez, B. A. Tucker, M. J. Young, I. Bravo-Osuna; PLGA Microparticles Loaded With Neuroprotective Agents (GDNF and BDNF). A Potential Treatment for Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5978.
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© ARVO (1962-2015); The Authors (2016-present)
The intravitreous administration of exogenous growth factors able to protect retinal ganglion cells (RGCs) has become a stimulating approach in the treatment of glaucoma. The aim of this work is the development and characterization of poly-(lactic-co-glycolic acid) (PLGA) microparticles loaded with GDNF and BDNF destined for intraocular administration.
MPs were prepared by the O/W emulsion-solvent evaporation technique. The O-phase consisted of 1ml of PLGA/CH2Cl2 solution 20%w/v in which GDNF (40µg) and BDNF (20µg) were added. After emulsification in PVA 0.1%w/v, MPs were hardening for 3h. Finally, MPs were recovered, washed with distilled water and frozen in MeOH/ice mixture before freeze-drying. Morphological and particle size characterization were performed by scanning electronic microscopy (SEM) and Coulter® Multisizer respectively. In vitro release of GDNF and BDNF from MPs was performed for 12 weeks in 1.5ml of a release media composed by PBS (pH 7.4) isotonized with NaCl, 1%BSA and 0.02% Sodium Azide. At pre-set times (1h, 24h and once a week for 12 weeks) the release medium was collected and GDNF/BDNF levels were quantified using ELISA.
The encapsulation efficiencies of MPs were 33.0±10.0% for GDNF and 25.9±4.8% for BDNF. MPs ranged from 2-40µm in size, were spherical in shape and had porous surfaces. An initial burst effect (24h of the release assay) was observed with values of 45.7±10.5ngGDNF/mgMPs and 11.2±0.5ngBDNF/mgMPs. Subsequently, MPs released amounts of 0.33±0.10ngGDNF/mgMPs/day and 0.30±0.03ngBDNF/mgMPs/day for two weeks. After that, an almost constant release of 31.4±10.7pgGDNF/mgMPs/day and 11.6±2.3pgBDNF/mgMPs/day was observed up to 7 weeks. Media collected during this time and tested using a ganglion cell survival assay was shown to be neuroprotective, indicating that both growth factors remained functional following PLGA degradation and release. From weeks 7 to 12 of the assay, MPs released of GDNF and BDNF were determined to be 18.1±1.2pg/mgMPs/day and 4.6±0.02pg/mgMPs/day respectively.
The MPs presented in this study provide a sustained controlled release of bioactive GDNF and BDNF for an extended period of time.
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