In vitro study of GDNF release from biodegradable PLGA microspheres

• Published in: Journal of controlled release Vol. 95; no. 3; pp. 463 - 475
• Main Authors: Aubert-Pouëssel, Anne, Venier-Julienne, Marie-Claire, Clavreul, Anne, Sergent, Michelle, Jollivet, Christophe, Montero-Menei, Claudia N., Garcion, Emmanuel, Bibby, David C., Menei, Philippe, Benoit, Jean-Pierre
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 24.03.2004; Elsevier
• Subjects: Alzheimer Disease - drug therapy; Animals; Biodegradation, Environmental - drug effects; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacology; Drug Evaluation, Preclinical - methods; Drug Stability; Enzyme-Linked Immunosorbent Assay - methods; Experimental design; GDNF; General pharmacology; Glial Cell Line-Derived Neurotrophic Factor; Iodine Radioisotopes; Lactic Acid - administration & dosage; Lactic Acid - chemistry; Materials Testing - methods; Medical sciences; Microspheres; Nerve Growth Factors - chemistry; Nerve Growth Factors - pharmacokinetics; Nerve Growth Factors - therapeutic use; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(lactic-co-glycolic acid); Polyglycolic Acid - administration & dosage; Polyglycolic Acid - chemistry; Polymers - administration & dosage; Polymers - chemistry; Polypropylenes - chemistry; Stabilization; Technology, Pharmaceutical - methods; Time Factors; PBS; CNTF; Stabilization; BDNF; EGF; CNS; KGF; NGF; .; TRIS; Microspheres; BSA; TGF; PLGA; GDNF; TH; Experimental design; HSA; Poly(lactic-co-glycolic acid); ELISA; Microsphere; Pharmaceutical technology; Biodegradability; Glycolic acid polymer; In vitro; Lactic acid polymer; Hydroxyacid; Glycolic acid; Copolymer; Lactic acid; Release
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2003.12.012

Glial cell line-derived neurotrophic factor (GDNF) is a protein with potent trophic actions on dopaminergic neurons, which is under investigation as a therapeutic agent for the treatment of neurodegenerative disorders, including Parkinson's disease. The aim of this work was to develop GDNF-loaded microspheres, which could be implanted by stereotaxy in the brain and could offer an alternative strategy in the treatment of Parkinson's disease. A w/o/w extraction–evaporation technique was chosen to prepare protein-loaded microspheres. An in vitro release study of the protein was required to assess the retention of integrity and the performance of the microsphere formulation with regard to sustained release. In order to assess the in vitro release profile of the GDNF-loaded microspheres, a preliminary study was performed to select an appropriate buffer for GDNF stabilization, using experimental designs. GDNF was measured by both enzyme-linked immunosorbant assay (ELISA) and radioactivity using 125I-GDNF. The GDNF-loaded microsphere release profile was assessed in a low continuous flow system, and showed a sustained release over 56 days of biologically active GDNF at clinically relevant doses.