(683a) Development of Injectable Microgels for Galns Enzyme Replacement Therapy

Introduction: In this study, we developed injectable microgels comprised of multiarm polyethylene glycol acrylate (PEG-Ac) with tunable degradation and controlled release features. We employed the microgels for the encapsulation and delivery of N-acetylgalactosamineâ?6â?sulfate sulfatase (GALNS) enzyme with the broader goal of developing an effective enzyme replacement therapy. Deficiency of GALNS causes accumulation of glycosoaminoglycans and ultimately Morquio A disease. Although effective in alleviating some disease symptoms, current enzyme replacement therapy (ERT) has many limitations, such as a need for recurrent infusions and occurrence of immune responses.¹ Delivery of GALNS encapsulated in PEG microgels could offer an improvement over existing therapies, as it preserves enzyme activity, leads to longer circulation times and attenuates immune responses, while requiring a single injection.

The PEG microgels in this study were prepared by electrospraying by Michaelâ??s addition reaction. We were able to obtain microgels of size range 70-300 µm by varying the electrospraying set-up parameters. The microgels could be injected through a needle, while still preserving their integrity upon injection. Further, the degradation of the microgels could be tuned to control release of encapsulated proteins. Release kinetics for several model proteins varying in size and hydrodynamic radii was found to be dependent on the protein size, as well as mesh size and degradation rate of the hydrogel. Furthermore, we observed preservation of GALNS enzyme activity in the upon encapsulation in the microgels. The nanoporous microgel mesh size precluded protein release until sufficient microgel degradation occurred.

Conclusions: The developed drug delivery approach has potential as a modified-ERT system to improve treatment outcomes and quality of life of Morquio A patients.

References: 1. Montaño, A. M.; Tomatsu, S.; Gottesman, G. S.; Smith, M.; Orii, T. International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. Journal of inherited metabolic disease 2007, 30, (2), 165-74.