Controlled release of glial cell line-derived neurotrophic factor from poly(ε-caprolactone) microspheres

Glial cell line-derived neurotrophic factor (GDNF), a growth factor expressed in the central nervous system, promotes the survival of both dopaminergic and motor neurons, making it a promising candidate for neurodegenerative disease therapy. Although GDNF is currently being evaluated in clinical trials for the treatment of Parkinson's disease (PD), the current delivery method using catheter implantation has certain limitations in terms of delivering GDNF safely and effectively. As a proof of concept, we encapsulated GDNF into poly(ε-caprolactone) (PCL) microspheres to enable controlled drug release for 25 days. First, microspheres were loaded with bovine serum albumin (BSA) to determine the optimal fabrication conditions necessary to achieve the desired release rates of protein. BSA was then used as a carrier protein to preserve GDNF activity during the fabrication process in the presence of organic solvents. GDNF-encapsulated microspheres were created and characterized using scanning electron microscopy. Next, the in vitro release of GDNF along with microsphere morphology was tracked over 25 days. Finally, the bioactivity of the released GDNF was confirmed using PC12 cells. This work demonstrates the potential of such microspheres for the delivery of bioactive GDNF with the end goal of developing a suitable, clinically relevant formulation for injection to appropriate regions of the brain in PD patients.