title: Biodegradable microparticles for strictly regulating the release of neurotrophic factors.
abstract: A lot of research has been carried out in the last decade to find a cure for neurodegenerative diseases especially Parkinson's disease but to little avail. In this study we have demonstrated the use of poly(lactic-co-glycolic acid) (PLGA)/collagen biodegradable microparticles formed using water-in-oil-in-water (W/O/W) double emulsion method, as a neurotrophic factor delivery vehicle. The microparticles were encapsulated with glial cell-derived neurotrophic factor (GDNF) fused with collagen binding peptide (CBP) immobilized to the inner collagen phase. The novelty lies in the strict regulation of release of GDNF-CBP from the microparticles as compared to a burst release from standard microparticles. The microparticles were demonstrated to be non-cytotoxic till 300 μg/2 × 10⁵ cells and revealed a maximum release of 250 ng GDNF-CBP/mg microparticles in 0.3% collagenase. Differentiation of neural progenitor cells (NPCs) into mature neurons was demonstrated by co-culturing microparticles with cells in a medium containing collagenase which enabled the release of encapsulated GDNF-CBP, signaling the differentiation of NPCs into microtubule-associated protein 2 (MAP2)-expressing neurons. The successful ability of these microparticles to deliver neurotrophic factors and allow differentiation of NPCs into mature neurons provides some scope in its use for the treatment of Parkinson's disease and other neurodegenerative diseases.
authors.affiliation: Frontier Research Core for Life Sciences, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Gujral
authors.forename: Y
authors.initials: Y
authors.lastname: Minagawa
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: H
authors.initials: H
authors.lastname: Kitano
authors.forename: T
authors.initials: T
authors.lastname: Nakaji-Hirabayashi
mesh_terms: D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C571744:bone sialoprotein (35-62), human; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen