Highly versatile polyelectrolyte complexes for improving the enzyme replacement therapy of lysosomal storage disorders

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 -galactos...

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Detalles Bibliográficos
Autores: Giannotti, M. I., Abasolo, Ibane|||0000-0001-5970-6276, Oliva, Mireia, Andrade, Fernanda|||0000-0002-4947-2346, García Aranda, Natalia|||0000-0003-3230-9881, Melgarejo, Marta, Pulido, Daniel|||0000-0002-2841-194X, Corchero Nieto, José Luis|||0000-0002-6109-144X, Fernández Caparrós, Yolanda, Villaverde, Antonio|||0000-0002-2615-4521, Royo, Miriam|||0000-0001-5292-0819, García Parajó, María F.., Sanz, Fausto, Schwartz, Simon|||0000-0001-8297-7971
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:174141
Acceso en línea:https://ddd.uab.cat/record/174141
https://dx.doi.org/urn:doi:10.1021/acsami.6b08356
Access Level:acceso abierto
Palabra clave:Enzyme replacement therapy
Fabry disease
Lysosomal delivery
Nanomedicine
Polyelectrolyte complexes
Trimethyl chitosan
α-galactosidase A
Descripción
Sumario: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.

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