In vitro study of GDNF release from biodegradable PLGA microspheres.
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.
Aubert-Pouëssel
Anne
A
INSERM ERIT-M 0104, Ingénierie de la Vectorisation Particulaire, IBT, 10 rue André Boquel, 49 100, Angers, France.
Venier-Julienne
Marie-Claire
MC
Clavreul
Anne
A
Sergent
Michelle
M
Jollivet
Christophe
C
Montero-Menei
Claudia N
CN
Garcion
Emmanuel
E
Bibby
David C
DC
Menei
Philippe
P
Benoit
Jean-Pierre
JP
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001673:Biodegradation, Environmental / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007457:Iodine Radioisotopes; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry*; D008422:Materials Testing / Q000379:methods; D008863:Microspheres; D009414:Nerve Growth Factors / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011126:Polypropylenes / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
D003692:Delayed-Action Preparations; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors; D011108:Polymers; D011126:Polypropylenes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid