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 cross-linked polyelectrolyte complex (PEC) composed of trimethyl chitosan (TMC) and α-galacto...

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Detalles Bibliográficos
Autores: Giannotti, Marina Inés, Abasolo, Ibane, Oliva, Mireia (Oliva Herrera), Andrade, Fernanda, García-Aranda, Natalia, Melgarejo Diaz, Marta, Pulido, Daniel, Corchero, José L., Fernández Amurgo, Yolanda, Villaverde, Antonio, Royo Expósito, Miriam, García-Parajo, María F., Sanz Carrasco, Fausto, Schwartz Navarro, Simó
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/116163
Acceso en línea:https://hdl.handle.net/2445/116163
Access Level:acceso abierto
Palabra clave:Errors congènits del metabolisme
Lisosomes
Nanomedicina
Inborn errors of metabolism
Lysosomes
Nanomedicine
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 cross-linked polyelectrolyte complex (PEC) composed of trimethyl chitosan (TMC) and α-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 untargeted 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 freeze-drying 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 the activity of the therapeutic protein to remain intact. 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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