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

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Abstract

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.

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Acknowledgments

The authors would like to acknowledge the support from an NSERC Discovery Grant (S.M.W.) and an NSERC Engage Grant with MedGenesis Therapeutix. They would also like to acknowledge the Advanced Microscopy Facility at the University of Victoria and MedGenesis Therapeutix for their ongoing support of this project.

Conflict of interest

The corresponding author previously held an Engage Grant with MedGenesis Therapeutix, and MedGenesis Therapeutix supported this project via donation of GDNF.

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  1. University of Victoria, Victoria, BC, Canada

    Andrew Agbay, Nima Khadem Mohtaram & Stephanie Michelle Willerth

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  1. Andrew Agbay
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Correspondence to Stephanie Michelle Willerth.

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Agbay, A., Mohtaram, N.K. & Willerth, S.M. Controlled release of glial cell line-derived neurotrophic factor from poly(ε-caprolactone) microspheres. Drug Deliv. and Transl. Res. 4, 159–170 (2014). https://doi.org/10.1007/s13346-013-0189-0

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