Purchase this article with an account.
P. Checa, B. A. Tucker, I. T. Molina-Martinez, M. J. Young, I. Bravo-Osuna, R. Herrero-Vanrell; Release Rate of Gdnf From Plga Microspheres for the Treatment of Neural Degenerative Diseases. Influence of Vitamin E Addition. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4514.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
α-tocoferol acetate (Vit E) is a protective (antioxidation and antiproliferation) endogenous component of retinal tissue. Its combination with GDNF provides a potential strategy for the development of long-term sustained release microspheres (MSs) that can be used, via transplantation, to treat retina degenerative disease. In this study, the influence of different amounts of Vit E on the release behaviour of GDNF from MSs was studied.Materials&
Materials:PLGA 50:50 (Resomer® 503) (Boehringer Ingelheim), α-tocoferol acetate (Vit E) (Sigma-Aldrich), GDNF (R&D).Methods: MSs were prepared by the O/W emulsion-solvent evaporation method employing 20µg of GDNF and 20µl (Formulation A) or 40µl (Formulation B) of Vit E. Morphological and particle size characterization were performed by scanning electronic microscopy (SEM) and Coulter® Multisizer respectively. In vitro release studies of GDNF from MSs were performed for 18 weeks. At pre-set times (1h, 24h and once a week for 18 weeks) the release medium (1.5ml of PBS 7.4 isotonized with NaCl) was collected and GDNF levels quantified using ELISA. The functionality of GDNF released from the MSs was evaluated in vitro via a retinal ganglion cell survival assay at 1h, 4 weeks and 7 weeks post- release.
The production yield (68.8% for formulation A, 65.9% for formulation B) and MSs size distribution (the 2-40µm range) was similar for both of the formulations tested. A different initial burst effect (1h release assay) was observed between formulation A and formulation B with values of 10.3±0.8ngGDNF/mgMSs (36.9±2.9% of final release) and 6.7±1.5 ngGDNF/mgMSs (28.0±5.6% of final release) respectively. In both cases, 90% of GDNF was released during the first 9 weeks of the release assay. A significant increase in retinal ganglion survival was detected in cultures treated with the release media containing GDNF as compared to control.
Vit E, when encapsulated in combination with GDNF, aids in the sustained controlled release of functional growth factor from PLGA MSs. As such, the MSs presented here posses optimal characteristics for intraocular administration and treatment of retinal degeneration.
This PDF is available to Subscribers Only