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Title: Highly Versatile Polyelectrolyte Complexes for Improving the Enzyme Replacement Therapy of Lysosomal Storage Disorders
Author: Giannotti, Marina Ines
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
Keywords: Errors congènits del metabolisme
Inborn errors of metabolism
Issue Date: 9-Sep-2016
Publisher: American Chemical Society
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 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.
Note: Versió postprint del document publicat a:
It is part of: ACS Applied Materials & Interfaces, 2016, vol. 8, num. 39, p. 25741-25752
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ISSN: 1944-8244
Appears in Collections:Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Ciència dels Materials i Química Física)
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

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