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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: ACS APPLIED BIO MATERIALS; v. N/A, p. 13-pg., 2022-06-22.

Resumo

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)

• Processo FAPESP: 19/25645-0 - Sistemas nanostruturados bioinspirados e biomiméticos para administração via nasal: uma nova perspectiva para a terapia de glioblastoma
• Beneficiário: Natália Noronha Ferreira Naddeo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 20/12277-0 - Drug discovery contra doenças infecciosas humanas
• Beneficiário: Edmarcia Elisa de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/08820-0 - Inibidores da via de síntese de vitamina B6 entregues por associação com nanopartículas contra Plasmodium sp
• Beneficiário: Arne Kruger
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/26722-8 - Drug discovery contra doenças infecciosas humanos
• Beneficiário: Carsten Wrenger
• Modalidade de apoio: Auxílio à Pesquisa - Temático