Highly Versatile Polyelectrolyte Complexes for Improving the Enzyme Replacement Therapy of Lysosomal Storage Disorders
| Autor: | Marina I. Giannotti, Natalia García-Aranda, José Luis Corchero, Antonio Villaverde, Daniel Pulido, Maria F. Garcia-Parajo, Fernanda Andrade, Mireia Oliva, Fausto Sanz, Miriam Royo, Ibane Abasolo, Yolanda Fernández, Simó Schwartz, Marta Melgarejo |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
α-galactosidase A Materials science Lisosomes 02 engineering and technology Inborn errors of metabolism law.invention 03 medical and health sciences Drug Delivery Systems law medicine Moiety Humans General Materials Science Enzyme Replacement Therapy Cytotoxicity chemistry.chemical_classification Fabry disease Chitosan Errors congènits del metabolisme Enzyme replacement therapy Trimethyl chitosan 021001 nanoscience & nanotechnology medicine.disease Polyelectrolytes Polyelectrolyte Polyelectrolyte complexes Lysosomal delivery 030104 developmental biology Enzyme Nanomedicine Biochemistry chemistry Nanomedicina Recombinant DNA Fabry Disease 0210 nano-technology Lysosomes Intracellular |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| ISSN: | 1944-8252 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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