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 / Tancini, Brunella; Tosi, Giovanni; Bortot, Barbara; Dolcetta, Diego; Magini, Alessandro; De Martino, Eleonora; Urbanelli, Lorena; Ruozi, Barbara; Forni, Flavio; Emiliani, Carla; Vandelli, Maria Angela; Severini, Giovanni Maria. - In: JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY. - ISSN 1533-4880. - STAMPA. - 15:4(2015), pp. 2657-2666. [10.1166/jnn.2015.9251]

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

TOSI, Giovanni;RUOZI, Barbara;FORNI, Flavio;VANDELLI, Maria Angela;
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.
2015
15
4
2657
2666
Use of Polylactide-Co-Glycolide-Nanoparticles for Lysosomal Delivery of a Therapeutic Enzyme in Glycogenosis Type II Fibroblasts / Tancini, Brunella; Tosi, Giovanni; Bortot, Barbara; Dolcetta, Diego; Magini, Alessandro; De Martino, Eleonora; Urbanelli, Lorena; Ruozi, Barbara; Forni, Flavio; Emiliani, Carla; Vandelli, Maria Angela; Severini, Giovanni Maria. - In: JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY. - ISSN 1533-4880. - STAMPA. - 15:4(2015), pp. 2657-2666. [10.1166/jnn.2015.9251]
Tancini, Brunella; Tosi, Giovanni; Bortot, Barbara; Dolcetta, Diego; Magini, Alessandro; De Martino, Eleonora; Urbanelli, Lorena; Ruozi, Barbara; Forni, Flavio; Emiliani, Carla; Vandelli, Maria Angela; Severini, Giovanni Maria
File in questo prodotto:
File Dimensione Formato  
JNN Myozyme.pdf

Solo gestori archivio

Tipologia: Versione pubblicata dall'editore
Dimensione 480.11 kB
Formato Adobe PDF
480.11 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/994515
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 18
social impact