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Pàgina inicial > Articles > Articles publicats > Highly versatile polyelectrolyte complexes for improving the enzyme replacement therapy of lysosomal storage disorders |
Data: | 2016 |
Resum: | 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. |
Ajuts: | Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1251 Ministerio de Economía y Competitividad SAF2014-60138-R Ministerio de Economía y Competitividad CTQ2015-66194-R Ministerio de Economía y Competitividad SEV-2015-0522 |
Drets: | Tots els drets reservats. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Enzyme replacement therapy ; Fabry disease ; Lysosomal delivery ; Nanomedicine ; Polyelectrolyte complexes ; Trimethyl chitosan ; α-galactosidase A |
Publicat a: | ACS applied materials & interfaces, Vol. 8 Núm 39 (Octubre 2016) , p. 25741-25752, ISSN 1944-8252 |
Post-print 47 p, 816.8 KB |