May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
gDNF-loaded PLGA Microparticles for Glaucoma Treatment: In vitro Release Studies
Author Affiliations & Notes
  • R. Herrero-Vanrell
    Department of Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain
  • P. Checa-Casalengua
    Department of Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain
  • S. Sacristán
    Department of Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain
  • I. T. Molina-Martinez
    Department of Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain
  • M. F. Refojo
    Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • M. J. Young
    Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • I. Bravo-Osuna
    Department of Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain
  • Footnotes
    Commercial Relationships  R. Herrero-Vanrell, None; P. Checa-Casalengua, None; S. Sacristán, None; I.T. Molina-Martinez, None; M.F. Refojo, None; M.J. Young, None; I. Bravo-Osuna, None.
  • Footnotes
    Support  BIOAVAN-PROFIT SINGULAR (PSS-300-100) and MAT2007-65288, Spanish Ministry of Education.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3177. doi:https://doi.org/
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      R. Herrero-Vanrell, P. Checa-Casalengua, S. Sacristán, I. T. Molina-Martinez, M. F. Refojo, M. J. Young, I. Bravo-Osuna; gDNF-loaded PLGA Microparticles for Glaucoma Treatment: In vitro Release Studies. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3177. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Among the new strategies in the treatment of ocular diseases as glaucoma, the intravitreous administration of neurotrophic factors is acquiring attention as one of the main promising candidates. The aim of this work is the evaluation of the in vitro release of glial-cell-line-derived neurotrophic factor (gDNF) from poly lactic-co-glycolic acid microparticles (PLGA MPs) destined to intraocular administration.

Methods: : PLGA microparticles loaded with gDNF were prepared according to the O/W emulsion-solvent evaporation technique modified by Herrero-Vanrell and Refojo (US Patent # 5,718,922). Microparticles were elaborated with initial gDNF amounts of 10 µg (formulation 1; F1) and 20 µg (formulation 2; F2). The neurotrophic factor was dispersed in an oil (α-tocopherol) in the inner phase of the starting emulsion. Morphological and particle size characterization were carried out by scanning electronic microscopy (SEM) and Coulter® Multisizer respectively. In vitro release of gDNF from MPs (5 mg) was performed by suspending them in 1.5 ml of PBS (pH 7.4; 0.1% BSA) at 37ºC for 5 weeks. At pre-set times (1 h, 1 day, 1, 2, 3, 4 and 5 weeks) the supernatant was removed and gDNF was quantified by the ELISA technique.

Results: : The production yield resulted high for both formulations (69-73%). Size distribution studies demonstrated that the mean proportion of MPs was in the 20-40 µm range. Microparticles were spherical and well defined, showing a porous surface. An initial burst effect (first hour of the release assay) was observed with values of 5.8±0.5 and 6.0±0.4 ng/mgMPs for F1 and F2 respectively. Subsequently, the amounts of released gDNF at 24h were 10.4±0.4 ng/mgMPs for F1 and 9.9±1.1 ng/mgMPs for F2. Since that time, a constant protein release was monitored up to 5 weeks at an almost constant rate of 92 and 119 pg/mgMP/day for F1 and F2 correspondingly.

Conclusions: : The PLGA microparticles presented in this work can control the gDNF release for an extended period of time.

Keywords: neuroprotection • vitreous • retina 
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