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Modulating Fingolimod (FTY720) Anti-SARS-CoV-2 Activity Using a PLGA-Based Drug Delivery System
Renata Rank Miranda1, Natália Noronha Ferreira1, Edmarcia Elisa de Souza2
1Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos, São Paulo University, Avenida Trabalhador São Carlense, 400, 13566-590 São Carlos, São Paulo, Brazil.
ACS Applied Bio Materials
|June 22, 2022
Summary
Nanotechnology enhances fingolimod (FTY720) for COVID-19 treatment. Encapsulated fingolimod in nanoparticles (NP@FTY720) shows reduced toxicity and significantly higher anti-SARS-CoV-2 activity compared to the free drug.
Area of Science:
- Nanomedicine
- Drug Repurposing
- Virology
Background:
- COVID-19 remains a global health crisis with over 490 million infections and 6 million deaths.
- While vaccines are crucial, effective treatments for existing COVID-19 cases are still needed.
- Drug repurposing combined with nanotechnology offers a promising therapeutic strategy.
Purpose of the Study:
- To develop a novel nanotechnology-based therapy for COVID-19 by repurposing fingolimod (FTY720).
- To encapsulate FTY720 into poly(lactic-co-glycolic acid) nanoparticles (NPs) for improved delivery and efficacy.
Main Methods:
- PLGA nanoparticles (NPs) were formulated to encapsulate FTY720, creating NP@FTY720.
- Physicochemical properties, drug release kinetics (pH-dependent), cytotoxicity, cellular uptake pathways (caveolin-mediated endocytosis, macropinocytosis), and anti-SARS-CoV-2 activity were evaluated.
- Flow cytometry and confocal microscopy were used to study NP internalization and localization.
Main Results:
- NP@FTY720 nanoparticles measured approximately 150 nm with high drug entrapment efficiency (~90%).
- NP@FTY720 demonstrated pH-dependent FTY720 release and significantly lower cytotoxicity compared to free FTY720.
- NPs were efficiently internalized via specific endocytic pathways and co-localized with lysosomes.
- NP@FTY720 exhibited potent anti-SARS-CoV-2 activity, with nearly 70-fold higher efficacy than free FTY720 at non-cytotoxic concentrations.
Conclusions:
- The novel NP@FTY720 formulation represents a promising nanotechnology-based approach for COVID-19 treatment.
- This strategy combines drug repurposing with advanced nanoparticle delivery for enhanced therapeutic potential.
- NP@FTY720 offers a potential frontline therapy against SARS-CoV-2 infection.
