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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
Other authors:	Universitat de Barcelona
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.
Subject(s):	-Errors congènits del metabolisme -Lisosomes -Nanomedicina -Inborn errors of metabolism -Lysosomes -Nanomedicine
Rights:	(c) American Chemical Society , 2016
Document type:	Article Article - Accepted version
Published by:	American Chemical Society
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