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

Renata Rank Miranda | Zendy; Natália Noronha Ferreira | Zendy; Edmárcia Elisa de Souza | Zendy; Paula Maria Pincela Lins | Zendy; Leonardo Miziara Barboza Ferreira | Zendy; Arne Krüger | Zendy; Valéria Maria de Oliveira Cardoso | Zendy; Edison Luíz Durigon | Zendy; Carsten Wrenger | Zendy; Valtencir Zucolotto | Zendy

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

Author(s) -

Renata Rank Miranda,

Natália Noronha Ferreira,

Edmárcia Elisa de Souza,

Paula Maria Pincela Lins,

Leonardo Miziara Barboza Ferreira,

Arne Krüger,

Valéria Maria de Oliveira Cardoso,

Edison Luíz Durigon,

Carsten Wrenger,

Valtencir Zucolotto

Publication year - 2022

Publication title -

acs applied bio materials

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.764

H-Index - 17

ISSN - 2576-6422

DOI - 10.1021/acsabm.2c00349

Subject(s) - drug repositioning , fingolimod , drug , repurposing , drug delivery , covid-19 , endocytosis , pharmacology , pinocytosis , flow cytometry , plga , cytotoxicity , chemistry , virology , nanotechnology , medicine , infectious disease (medical specialty) , biology , cell , nanoparticle , immunology , disease , biochemistry , multiple sclerosis , materials science , in vitro , ecology , pathology

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. Nanoparticles (NPs) based on PLGA for fingolimod (FTY720) encapsulation show a size of ∼150 nm and high drug entrapment (∼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.

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