DataVXACS Applied Materials & InterfacesPaper
journal article·2016-10-05Open access

Highly Versatile Polyelectrolyte Complexes for Improving the Enzyme Replacement Therapy of Lysosomal Storage Disorders

Marina I. Giannotti, Ibane Abasolo, Mireia Oliva, Fernanda Andrade, Natalia García-Aranda, Marta Melgarejo, Daniel Pulido, José L. Corchero, Yolanda Fernández, Antonio Villaverde, Miriam Royo, María F. García-Parajo, Fausto Sanz, Simó Schwartz

ACS Applied Materials & Interfaces· Volume 8· Issue 39
Publisher pageOpen full text
Source abstract

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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Lysosomal Storage Disorders Research · Autoimmune and Inflammatory Disorders Research · Complement system in diseases

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Centro de Investigación Biomédica en Red—Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain

Nanoprobes & Nanoswitches, Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 10, 08028 Barcelona, Spain

Physical Chemistry Department, Universitat de Barcelona, 08028 Barcelona, Spain

CIBBIM-Nanomedicine, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain

Pharmacy and Pharmaceutical Technology Department, Universitat de Barcelona, 08028 Barcelona, Spain

Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal

Combinatorial Chemistry Unit, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain

Institut de Biotecnologia i de Biomedicina and Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Cerdanyola del Vallès, Spain

Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain

Funding

Generalitat de Catalunya · Instituto de Salud Carlos III · Ministerio de Econom??a y Competitividad

References (60)

Show source-provided references
1. 10.1038/nrm142310.1038/nrm1423 ↗
2. Fabry Disease: Perspectives from 5 Years of FOS.Oxford PharmaGenesis: 2006.
3. 10.1517/21678707.2013.78097010.1517/21678707.2013.780970 ↗
4. 10.1021/nn402753y10.1021/nn402753y ↗
5. 10.1021/bm200338410.1021/bm2003384 ↗
6. 10.1016/j.jconrel.2014.08.01510.1016/j.jconrel.2014.08.015 ↗
7. 10.1016/S1369-7021(05)71033-610.1016/S1369-7021(05)71033-6 ↗
8. 10.1016/j.jconrel.2011.06.00110.1016/j.jconrel.2011.06.001 ↗
9. 10.1038/nrd289710.1038/nrd2897 ↗
10. 10.1021/nn507382n10.1021/nn507382n ↗
11. 10.1002/adhm.20150074610.1002/adhm.201500746 ↗
12. 10.1039/C4OB01153H10.1039/C4OB01153H ↗
13. 10.1016/j.colsurfb.2012.07.01310.1016/j.colsurfb.2012.07.013 ↗
14. 10.1021/bc200594510.1021/bc2005945 ↗
15. 10.1039/C4CC09829C10.1039/C4CC09829C ↗
16. 10.1021/bc200336j10.1021/bc200336j ↗
17. 10.1021/mp300293n10.1021/mp300293n ↗
18. 10.1038/nrg96310.1038/nrg963 ↗
19. 10.1056/NEJM19670525276210110.1056/NEJM196705252762101 ↗
20. 10.1126/science.167.3922.126810.1126/science.167.3922.1268 ↗
21. 10.1073/pnas.071230910510.1073/pnas.0712309105 ↗
22. 10.1002/iub.48710.1002/iub.487 ↗
23. 10.1038/mt.2008.12710.1038/mt.2008.127 ↗
24. 10.7150/thno/v01p018910.7150/thno/v01p0189 ↗
25. 10.1016/S1525-0016(02)90721-510.1016/S1525-0016(02)90721-5 ↗
26. 10.1021/mp300273310.1021/mp3002733 ↗
27. 10.1021/bm060967g10.1021/bm060967g ↗
28. 10.1016/S0144-8617(98)00009-510.1016/S0144-8617(98)00009-5 ↗
29. 10.1016/j.biomaterials.2008.05.02610.1016/j.biomaterials.2008.05.026 ↗
30. 10.1039/C5TB01345C10.1039/C5TB01345C ↗
31. 10.1016/S0040-4039(00)01060-110.1016/S0040-4039(00)01060-1 ↗
32. 10.1002/chem.20080006510.1002/chem.200800065 ↗
33. 10.1002/btpr.63710.1002/btpr.637 ↗
34. 10.1007/s11051-014-2292-710.1007/s11051-014-2292-7 ↗
35. 10.1016/j.jconrel.2011.06.03910.1016/j.jconrel.2011.06.039 ↗
36. Desnick R. J. · J. Lab. Clin. Med. · 1973 · 81 · 157
37. 10.1016/0009-8981(81)90384-310.1016/0009-8981(81)90384-3 ↗
38. 10.1681/ASN.200504038310.1681/ASN.2005040383 ↗
39. 10.1073/pnas.94.6.254010.1073/pnas.94.6.2540 ↗
40. 10.2147/IJN.S3611110.2147/IJN.S36111 ↗
41. 10.1111/1523-1747.ep1261374810.1111/1523-1747.ep12613748 ↗
42. 10.1016/j.eurpolymj.2016.06.00310.1016/j.eurpolymj.2016.06.003 ↗
43. Dean K. J. · J. Biol. Chem. · 1979 · 254 · 999410.1016/S0021-9258(19)86663-2 ↗
44. 10.1016/j.jmb.2004.01.03510.1016/j.jmb.2004.01.035 ↗
45. 10.1021/nn700256c10.1021/nn700256c ↗
46. 10.1016/j.jconrel.2005.11.01410.1016/j.jconrel.2005.11.014 ↗
47. 10.1016/j.jfda.2014.10.00810.1016/j.jfda.2014.10.008 ↗
48. 10.1038/nmat244210.1038/nmat2442 ↗
49. 10.1016/j.biomaterials.2009.03.01310.1016/j.biomaterials.2009.03.013 ↗
50. 10.1007/s10856-008-3659-z10.1007/s10856-008-3659-z ↗
51. Raub T. J. · J. Cell Sci. · 1990 · 97 · 12710.1242/jcs.97.1.127 ↗
52. 10.1016/S0009-8981(98)00169-710.1016/S0009-8981(98)00169-7 ↗
53. 10.1074/jbc.M112.36938910.1074/jbc.M112.369389 ↗
54. 10.1016/j.jconrel.2010.10.03110.1016/j.jconrel.2010.10.031 ↗
55. 10.1016/j.ymthe.2005.07.68710.1016/j.ymthe.2005.07.687 ↗
56. 10.1016/j.biomaterials.2009.11.02810.1016/j.biomaterials.2009.11.028 ↗
57. 10.1073/pnas.030872810010.1073/pnas.0308728100 ↗
58. 10.1016/j.ymgme.2014.08.00210.1016/j.ymgme.2014.08.002 ↗
59. 10.1371/journal.pone.013434110.1371/journal.pone.0134341 ↗
60. 10.1016/j.carbpol.2015.01.04810.1016/j.carbpol.2015.01.048 ↗