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Highly versatile polyelectrolyte complexes for improving the enzyme replacement therapy of lysosomal storage disorders.
Giannotti, MI (Universitat de Barcelona. Departament de Química física)
Abasolo, Ibane (Universitat Autònoma de Barcelona. Vall d'Hebron Institut de Recerca)
Oliva, Mireia (Universitat de Barcelona. Departament de Farmàcia i Tecnologia Farmacèutica, i Fisicoquímica)
Andrade, Fernanda (Universitat de Barcelona. Departament de Farmàcia i Tecnologia Farmacèutica, i Fisicoquímica)
García-Aranda, Natalia (Universitat Autònoma de Barcelona. Vall d'Hebron Institut de Recerca)
Melgarejo, Marta (Combinatorial Chemistry Unit, Barcelona Science Park (Baldiri Reixac))
Pulido, Daniel (Combinatorial Chemistry Unit, Barcelona Science Park (Baldiri Reixac))
Corchero Nieto, José Luis (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Fernández, Yolanda (Universitat Autònoma de Barcelona. Vall d'Hebron Institut de Recerca)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Royo, Miriam (Combinatorial Chemistry Unit, Barcelona Science Park (Baldiri Reixac))
Garcia-Parajo, Maria F. (Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology)
Sanz, Fausto (Combinatorial Chemistry Unit, Barcelona Science Park (Baldiri Reixac))
Simó Schwartz Jr (Universitat Autònoma de Barcelona. Vall d'Hebron Institut de Recerca)

Date: 2016
Abstract: Lysosomal storage disorders are currently treated by enzyme replacement therapy (ERT) through the direct administration of the unprotected recombinant protein to the patients. Herein we present an ionically crosslinked polyelectrolyte complex (PEC) composed of trimethyl chitosan (TMC) and -galactosidase A (GLA), the defective enzyme in Fabry disease, with the capability of directly targeting endothelial cells by incorporating peptide ligands containing the RGD sequence. We assessed the physicochemical properties, cytotoxicity and hemocompatibility of RGD-targeted and un-targeted PECs, the uptake by endothelial cells and the intracellular activity of PECs in cell culture models of Fabry disease. Moreover, we also explored the effect of different freezedrying procedures in the overall activity of the PECs. Our results indicate that the use of integrin-binding RGD moiety within the PEC increases their uptake and the efficacy of the GLA enzyme, while the freeze-drying allows keeping intact the activity of the therapeutic protein. Overall, these results highlight the potential of TMC-based PECs as a highly versatile and feasible drug delivery system for improving the ERT of lysosomal storage disorders.
Note: Número d'acord de subvenció AGAUR/2014/SGR-1251
Note: Número d'acord de subvenció MINECO/SAF2014-60138-R
Note: Número d'acord de subvenció MINECO/CTQ2015-66194-R
Note: Número d'acord de subvenció MINECO/SEV-2015-0522
Rights: Tots els drets reservats.
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Enzyme replacement therapy ; Fabry disease ; Lysosomal delivery ; Nanomedicine ; Polyelectrolyte complexes ; Trimethyl chitosan ; α-galactosidase A
Published in: ACS applied materials & interfaces, Vol. 8 Núm 39 (Octubre 2016) , p. 25741-25752, ISSN 1944-8244

DOI: 10.1021/acsami.6b08356


Post-print
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Articles > Research articles
Articles > Published articles

 Record created 2017-04-25, last modified 2019-09-26



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