Glycogenosis type II, or Pompe Disease, is a lysosomal storage disease caused by the deficiency of acid alpha-glucosidase (GAA), leading to glycogen accumulation in muscles. A recombinant human GAA (rhGAA, Myozyme®) is currently used for enzyme replacement therapy. Despite its efficacy in most of patients, some of them show a diminished response to the treatment with rapidly progressive clinical deterioration, due to immuno-mediated enzyme inactivation. To demonstrate that Nanoparticles (NPs) could be profitably exploited to carry macromolecules, PLGA NPs loaded with rhGAA (GAA-NPs) were prepared by double emulsion solvent evaporation. Their surface morphology, particle size, zeta-potential and biochemical activity were assessed. "Pulse and chase" experiments were made by administrating GAA-NPs on patients' fibroblasts. Biochemical activity tests showed a more efficient cellular uptake of rhGAA loaded to NPs and a more significant stability of the enzyme (up to 7 days) in vitro, if compared to the same amount of rhGAA free enzyme. This data allows to envision in vivo experiments, in significant animal models, to further characterize lysosomal enzyme loaded-NPs' efficacy and toxicity.

Use of Polylactide-Co-Glycolide-Nanoparticles for Lysosomal Delivery of a Therapeutic Enzyme in Glycogenosis Type II Fibroblasts

DE MARTINO, ELEONORA;
2015

Abstract

Glycogenosis type II, or Pompe Disease, is a lysosomal storage disease caused by the deficiency of acid alpha-glucosidase (GAA), leading to glycogen accumulation in muscles. A recombinant human GAA (rhGAA, Myozyme®) is currently used for enzyme replacement therapy. Despite its efficacy in most of patients, some of them show a diminished response to the treatment with rapidly progressive clinical deterioration, due to immuno-mediated enzyme inactivation. To demonstrate that Nanoparticles (NPs) could be profitably exploited to carry macromolecules, PLGA NPs loaded with rhGAA (GAA-NPs) were prepared by double emulsion solvent evaporation. Their surface morphology, particle size, zeta-potential and biochemical activity were assessed. "Pulse and chase" experiments were made by administrating GAA-NPs on patients' fibroblasts. Biochemical activity tests showed a more efficient cellular uptake of rhGAA loaded to NPs and a more significant stability of the enzyme (up to 7 days) in vitro, if compared to the same amount of rhGAA free enzyme. This data allows to envision in vivo experiments, in significant animal models, to further characterize lysosomal enzyme loaded-NPs' efficacy and toxicity.
http://www.ingentaconnect.com/content/asp/jnn/2015/00000015/00000004
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2893710
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