In vitro study of GDNF release from biodegradable PLGA microspheres

• DOI: 10.1016/j.jconrel.2003.12.012
• Publication Date: 2004-02-06T05:17:37Z
• Authors: Anne Aubert-Pouëssel; Marie-Claire Veni...; Anne Clavreul; Michelle Sergent; Christophe Jollivet; Claudia N. Monter...; Emmanuel Garcion; David C. Bibby; Philippe Menei; Jean-Pierre Benoit
• Keywords: 0301 basic medicine; 0303 health sciences; Time Factors; Polymers; Chemistry, Pharmaceutical; Drug Evaluation, Preclinical; Enzyme-Linked Immunosorbent Assay; Polypropylenes; Microspheres; Iodine Radioisotopes; 03 medical and health sciences; Biodegradation, Environmental; Drug Stability; Polylactic Acid-Polyglycolic Acid Copolymer; Alzheimer Disease; Delayed-Action Preparations; Materials Testing; Animals; Technology, Pharmaceutical; Glial Cell Line-Derived Neurotrophic Factor; Lactic Acid; Nerve Growth Factors; Polyglycolic Acid

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 (125)I-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.