Event Title
Development of inhaled PLGA encapsulated Ivermectin for the treatment of SARS-CoV-2
Location
Suwanee, GA
Start Date
3-5-2022 1:00 PM
End Date
3-5-2022 4:00 PM
Description
OBJECTIVE:
SARS-CoV-2 is a global threat to public health because of its high rate of infection causing fatalities. The arrival of vaccines has provided relief, but newer strains of SARS-CoV-2 are difficult to contain. As such, there is an urgent need to repurpose FDA-approved drugs with proven activity against COVID-19 as therapeutics to prevent proliferation of the virus. Recently, we reported that ivermectin (IVM) inhibited 3-chymotrypsin-like protease (3CLpro), an enzyme vital to SARS-CoV-2 replication, with a half-maximal inhibitory concentration (IC50) of 21μM. However, when taken orally, under 2 μM of IVM reaches the lungs, which is less than the IC50 against 3CLpro. Hence, site-specific delivery of IVM to the lungs will yield better results. We propose to develop an inhaled form of IVM and indocyanine green (ICG) encapsulated Poly(lactic-co-glycolic acid) (PLGA) to deliver IVM to the respiratory tract.
METHODS:
We hypothesize that once the formulation is delivered, the presence of ICG will enable in vivo imaging of the nanoparticles, and IVM will inhibit 3CLpro to prevent viral replication. Particle size and morphology of the synthesized particles will be characterized via particle size analyzer and Scanning Electron Microscope (SEM). Fourier Transform Infrared (FTIR), Thermogravimetric Analysis, and Differential Scanning Calorimeter will be used to confirm the presence of IVM in the nanoparticles and the amount of IVM in the nanoparticles will be quantified using high-performance liquid chromatography (HPLC). The Aerodynamic Particle Size Distribution Profiles tests (APSD) will be used to investigate their deposition profile. The nanoparticles were synthesized via double emulsion method with 0.3% polyvinyl alcohol as surfactant.
RESULTS:
Particle size analysis revealed that PLGA, PLGA-ICG, and PLGA-IVM-ICG were 100, 160, and 175 nm, respectively, and SEM confirmed their spherical morphology. FTIR validated the presence of IVM in the nanoparticles, and, once completely analyzed, they will be characterized in vitro and in vivo. Finally, in vitro assays have shown approximately 60% inhibition of our formulations against the enzyme.
CONCLUSION:
In summary, our data suggests that these formulations will act as a successful drug delivery mechanism to deliver IVM directly to the lungs. Furthermore, the efficacy of this system in vitro has shown that there is a need for in vivo trials in the future.
Embargo Period
5-31-2022
Development of inhaled PLGA encapsulated Ivermectin for the treatment of SARS-CoV-2
Suwanee, GA
OBJECTIVE:
SARS-CoV-2 is a global threat to public health because of its high rate of infection causing fatalities. The arrival of vaccines has provided relief, but newer strains of SARS-CoV-2 are difficult to contain. As such, there is an urgent need to repurpose FDA-approved drugs with proven activity against COVID-19 as therapeutics to prevent proliferation of the virus. Recently, we reported that ivermectin (IVM) inhibited 3-chymotrypsin-like protease (3CLpro), an enzyme vital to SARS-CoV-2 replication, with a half-maximal inhibitory concentration (IC50) of 21μM. However, when taken orally, under 2 μM of IVM reaches the lungs, which is less than the IC50 against 3CLpro. Hence, site-specific delivery of IVM to the lungs will yield better results. We propose to develop an inhaled form of IVM and indocyanine green (ICG) encapsulated Poly(lactic-co-glycolic acid) (PLGA) to deliver IVM to the respiratory tract.
METHODS:
We hypothesize that once the formulation is delivered, the presence of ICG will enable in vivo imaging of the nanoparticles, and IVM will inhibit 3CLpro to prevent viral replication. Particle size and morphology of the synthesized particles will be characterized via particle size analyzer and Scanning Electron Microscope (SEM). Fourier Transform Infrared (FTIR), Thermogravimetric Analysis, and Differential Scanning Calorimeter will be used to confirm the presence of IVM in the nanoparticles and the amount of IVM in the nanoparticles will be quantified using high-performance liquid chromatography (HPLC). The Aerodynamic Particle Size Distribution Profiles tests (APSD) will be used to investigate their deposition profile. The nanoparticles were synthesized via double emulsion method with 0.3% polyvinyl alcohol as surfactant.
RESULTS:
Particle size analysis revealed that PLGA, PLGA-ICG, and PLGA-IVM-ICG were 100, 160, and 175 nm, respectively, and SEM confirmed their spherical morphology. FTIR validated the presence of IVM in the nanoparticles, and, once completely analyzed, they will be characterized in vitro and in vivo. Finally, in vitro assays have shown approximately 60% inhibition of our formulations against the enzyme.
CONCLUSION:
In summary, our data suggests that these formulations will act as a successful drug delivery mechanism to deliver IVM directly to the lungs. Furthermore, the efficacy of this system in vitro has shown that there is a need for in vivo trials in the future.