Effective GDNF brain delivery using microspheres—A promising strategy for Parkinson's disease
Open accessAbstract
Glial cell line-derived neurotrophic factor (GDNF) has shown promise in the treatment of neurodegenerative disorders of basal ganglia origin such us Parkinson's disease (PD). In this study, we investigated the neurorestorative effect of controlled GDNF delivery using biodegradable microspheres in an animal model with partial dopaminergic lesion. Microspheres were loaded with N-glycosylated recombinant GDNF and prepared using the Total Recirculation One-Machine System (TROMS). GDNF-loaded microparticles were unilaterally injected into the rat striatum by stereotaxic surgery two weeks after a unilateral partial 6-OHDA nigrostriatal lesion. Animals were tested for amphetamine-induced rotational asymmetry at different times and were sacrificed two months after microsphere implantation for immunohistochemical analysis. The putative presence of serum IgG antibodies against rat glycosylated GDNF was analyzed for addressing safety issues. The results demonstrated that GDNF-loaded microspheres, improved the rotational behavior induced by amphetamine of the GDNF-treated animals together with an increase in the density of TH positive fibers at the striatal level. The developed GDNF-loaded microparticles proved to be suitable to release biologically active GDNF over up to 5 weeks in vivo. Furthermore, none of the animals developed antibodies against GDNF demonstrating the safety of glycosylated GDNF use.
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GDNF-loaded microsphere increased TH-positive fibers in striatum and substantia nigra, suggesting neuroprotection and neurorestoration activity.
“Apart from this GDNF-loaded microsphere increase in TH-positive fibers in the striatum and substantia nigra, the results suggested neuroprotection and neurorestoration activity.129,130”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [130]
PLGA-MS-mediated GDNF release demonstrated antiparkinsonian effects, confirmed by improvement in amphetamine-induced rotational behavior test.
“Similar results were also observed by Garbayo et al., where PLGA-MS-mediated GDNF release demonstrated antiparkinsonian effects, as confirmed by the improvement in the amphetamine-induced rotational behavior test.130”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [130]
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- Authors
- Garbayo, E., Montero-Menei, C. N., Ansorena, E., Lanciego, J. L., Aymerich, M. S., & Blanco-Prieto, M. J.
- Affiliations
- Universidad de Navarra (ES)
- Centro de Investigación Médica Aplicada (ES)
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 135
- Issue
- 2
- Pages
- 119-126
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2075997145
- Cited by
- 150
- References
- 29
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 13 · 2019: 5 · 2018: 9 · 2017: 9 · 2016: 15 · 2015: 18 · 2014: 10 · 2013: 14 · 2012: 13
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- glial cell line-derived neurotrophic factor, Parkinson's disease, biodegradable microspheres, controlled drug delivery, 6-hydroxydopamine lesion, nigrostriatal degeneration, striatum, amphetamine-induced rotation, tyrosine hydroxylase, neurorestoration, immunogenicity
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Brain, Cell Differentiation, Corpus Striatum, Disease Models, Animal, Drug Carriers, Female, Glycosylation, Immunohistochemistry, Kinetics, Microspheres, Models, Neurological, Parkinson Disease, Particle Size, Polyglycolic Acid, Recombinant Proteins, Drug Delivery Systems, PC12 Cells, Rats, Sprague-Dawley, Fluorescent Antibody Technique, Indirect, Lactic Acid, Glial Cell Line-Derived Neurotrophic Factor, Rats
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