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Modulating Fingolimod (FTY720) Anti-SARS-CoV-2 Activity Using a PLGA-Based Drug Delivery System

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Author(s):
Miranda, Renata Rank ; Ferreira, Natalia Noronha ; de Souza, Edmarcia Elisa ; Pincela Lins, Paula Maria ; Barboza Ferreira, Leonardo Miziara ; Kruger, Arne ; de Oliveira Cardoso, Valeria Maria ; Durigon, Edison Luiz ; Wrenger, Carsten ; Zucolotto, Valtencir
Total Authors: 10
Document type: Journal article
Source: ACS APPLIED BIO MATERIALS; v. N/A, p. 13-pg., 2022-06-22.
Abstract

COVID-19 has resulted in more than 490 million people being infected worldwide, with over 6 million deaths by April 05th, 2022. Even though the development of safe vaccine options is an important step to reduce viral transmission and disease progression, COVID-19 cases will continue to occur, and for those cases, efficient treatment remains to be developed. Here, a drug repurposing strategy using nanotechnology is explored to develop a therapy for COVID-19 treatment. Nanopartides (NPs) based on PLGA for fingolimod (FTY720) encapsulation show a size of similar to 150 nm and high drug entrapment (similar to 90%). The NP (NP@FTY720) can control FTY720 release in a pH-dependent manner. Cytotoxicity assays using different cell lines show that NP@FTY720 displays less toxicity than the free drug. Flow cytometry and confocal microscopy reveal that NPs are actively internalized mostly through caveolin-mediated endocytosis and macropinocytosis pathways and co-localized with lysosomes. Finally, NP@FTY720 not only exhibits anti-SARS-CoV-2 activity at non-cytotoxic concentrations, but its biological potential for viral infection inhibition is nearly 70 times higher than that of free drug treatment. Based on these findings, the combination of drug repurposing and nanotechnology as NP@FTY720 is presented for the first time and represents a promising frontline in the fight against COVID-19. (AU)

FAPESP's process: 19/25645-0 - BIOINSPIRED AND BIOMIMETIC NANOSTRUCTURED SYSTEMS FOR NOSE-TO-BRAIN ADMINISTRATION: A NOVEL PERSPECTIVE FOR GLIOBLASTOMA THERAPY
Grantee:Natália Noronha Ferreira Naddeo
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 20/12277-0 - Drug discovery against human infectious diseases
Grantee:Edmarcia Elisa de Souza
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 18/08820-0 - Nanoparticle-assisted drug delivery of Vitamin B6 pathway inhibitors in malaria
Grantee:Arne Kruger
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 15/26722-8 - Drug discovery against human infectious diseases
Grantee:Carsten Wrenger
Support Opportunities: Research Projects - Thematic Grants