Use of polylactide-co-glycolide-nanoparticles for lysosomal delivery of a therapeutic enzyme in glycogenosis type II fibroblasts

Brunella Tancini, Giovanni Tosi, Barbara Bortot, Diego Dolcetta, Alessandro Magini, Eleonora De Martino, Lorena Urbanelli, Barbara Ruozi, Flavio Forni, Carla Emiliani, Maria A. Vandelli, Giovanni Maria Severini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2657-2666
Number of pages10
JournalJournal of Nanoscience and Nanotechnology
Volume15
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • Acid alpha glucosidase
  • Drug delivery.
  • Myozyme ®
  • Nanoparticles
  • PLGA
  • Pompe disease

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Chemistry(all)
  • Materials Science(all)
  • Bioengineering
  • Biomedical Engineering
  • Medicine(all)

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  • Cite this

    Tancini, B., Tosi, G., Bortot, B., Dolcetta, D., Magini, A., De Martino, E., Urbanelli, L., Ruozi, B., Forni, F., Emiliani, C., Vandelli, M. A., & Severini, G. M. (2015). Use of polylactide-co-glycolide-nanoparticles for lysosomal delivery of a therapeutic enzyme in glycogenosis type II fibroblasts. Journal of Nanoscience and Nanotechnology, 15(4), 2657-2666. https://doi.org/10.1166/jnn.2015.9251