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

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. 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.

Polymeric Nanoparticles (PNPs) as drug delivery systems for SARS-CoV-2

“…The NPs were fabricated through a single emulsion solvent evaporation technique, resulting in a positively charged system with reported sizes of approximately 400 and 190 nm for empty NPs and FTY720-NP, respectively. The system demonstrated a notable drug entrapment rate of 90%, with drug release being contingent upon pH [75]. The study found that drug release required an acidic environment, which the developed NPs can access through caveolin-mediated endocytosis and micropinocytosis pathways.…”

The Application of Biomaterials for the Vaccine, Treatment, and Detection of SARS-CoV-2

“… 163 Lopinavir (LPV), an antiviral drug, could be loaded into PLGA nanoparticles coated with macrophage membranes (PLGA-LPV@M) to reduce tissue viral loads in mouse models. 164 Other anti-inflammatory and antiviral drugs, such as celecoxib, 165 quinine, 166 oseltamivir-phosphate, 167 favipiravir, 168 and fingolimod, 169 could be coated on or encapsulated into PLGA polymeric nanoparticles.…”

PLGA Particles in Immunotherapy

“…Targeted delivery of antibiotics loaded to PLGA particles has been described in several studies to effectively treat bacterial infections and reduce the risk of resistance development [ 149 , 150 , 151 ]. In a similar fashion, encapsulation and delivery of anti-viral and immunomodulating drugs have been successfully explored using PLGA particles to fight viral infections [ 152 , 153 , 154 , 155 ]. Aside from the aforementioned tools for approaching infectious diseases, protective vaccinations represent one of the most effective medical tools up to date.…”