Journal article
Preservation of biological activity of glial cell line-derived neurotrophic factor (GDNF) after microencapsulation and sterilization by gamma irradiation
International Journal of Pharmaceutics, Vol.436(1-2), pp.545-554
10/15/2012
DOI: 10.1016/j.ijpharm.2012.07.019
PMID: 22828071
Abstract
A main issue in controlled delivery of biotechnological products from injectable biodegradable microspheres is to preserve their integrity and functional activity after the microencapsulation process and final sterilization. The present experimental work tested different technological approaches to maintain the biological activity of an encapsulated biotechnological product within PLGA [poly (lactic-co-glycolic acid)] microspheres (MS) after their sterilization by gamma irradiation. GDNF (glial cell line-derived neurotrophic factor), useful in the treatment of several neurodegenerative diseases, was chosen as a labile model protein. In the particular case of optic nerve degeneration, GDNF has been demonstrated to improve the damaged retinal ganglion cells (RGC) survival. GDNF was encapsulated in its molecular state by the water-in-oil-in-water (W/O/W) technique or as solid according to the solid-in-oil-in-water (S/O/W) method. Based on the S/O/W technique, GDNF was included in the PLGA microspheres alone (S/O/W 1) or in combination with an antioxidant (vitamin E, Vit E) (S/O/W 2). Microspheres were sterilized by gamma-irradiation (dose of 25kGy) at room and low (−78°C) temperatures. Functional activity of GDNF released from the different microspheres was evaluated both before and after sterilization in their potential target cells (retinal cells). Although none of the systems proposed achieved with the goal of totally retain the structural stability of the GDNF-dimer, the protein released from the S/O/W 2 microspheres was clearly the most biologically active, showing significantly less retinal cell death than that released from either W/O/W or S/O/W 1 particles, even in low amounts of the neurotrophic factor. According to the results presented in this work, the biological activity of biotechnological products after microencapsulation and sterilization can be further preserved by the inclusion of the active molecule in its solid state in combination with antioxidants and using low temperature (−78°C) during gamma irradiation exposure.
Details
- Title: Subtitle
- Preservation of biological activity of glial cell line-derived neurotrophic factor (GDNF) after microencapsulation and sterilization by gamma irradiation
- Creators
- P Checa-Casalengua - Dep. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Avd. Complutense s/n, Complutense University, Madrid 28040, SpainC Jiang - Schepens Eye Research Institute, Dep. of Ophthalmology, Harvard Medical School, Harvard University, 20 Staniford Street, Boston, MA 02114, USAI Bravo-Osuna - Dep. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Avd. Complutense s/n, Complutense University, Madrid 28040, SpainB.A Tucker - Institute for Vision Research, Dep. of Ophthalmology, Carver College of Medicine, University of Iowa, 4187 MERF, Iowa City, IA 52242, USAI.T Molina-Martínez - Dep. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Avd. Complutense s/n, Complutense University, Madrid 28040, SpainM.J Young - Schepens Eye Research Institute, Dep. of Ophthalmology, Harvard Medical School, Harvard University, 20 Staniford Street, Boston, MA 02114, USAR Herrero-Vanrell - Dep. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Avd. Complutense s/n, Complutense University, Madrid 28040, Spain
- Resource Type
- Journal article
- Publication Details
- International Journal of Pharmaceutics, Vol.436(1-2), pp.545-554
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.ijpharm.2012.07.019
- PMID
- 22828071
- ISSN
- 0378-5173
- eISSN
- 1873-3476
- Grant note
- DOI: 10.13039/501100004837, name: Spanish Ministry of Science and Innovation, award: MAT-2010-18242; name: Centro de Microscopía Electrónica Luis Bru (CAI, UCM)
- Language
- English
- Date published
- 10/15/2012
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983979979502771
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