A nanotechnological approach in the current therapy of COVID-19: model drug oseltamivir-phosphate loaded PLGA nanoparticles targeted with spike protein binder peptide of SARS-CoV-2

Abstract

Coronavirus disease 2019 (COVID-19) is today's most serious epidemic disease threatening the human race. The initial therapeutic approach of SARS-CoV-2 disease is based upon the binding the receptor-binding site of the spike protein to the host cell's ACE-2 receptor on the plasma membrane. In this study, it is aimed to develop a biocompatible and biodegradable polymeric drug delivery system that is targeted to the relevant receptor binding site and provides controlled drug release. Oseltamivir phosphate (OP) is an orally administered antiviral prodrug for primary therapy of the disease in biochemically activated carboxylate form (oseltamivir carboxylate OC). In the presented study, model drug OP loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) targeted with spike-binding peptide 1 (SBP1) of SARS-CoV-2 were designed to be used as an efficient and prolonged released antiviral drug delivery system. RY, EE, and DL values of the OP-loaded NPs produced by the solvent evaporation method were calculated to be 59.3%, 61.4%, and 26.9%, respectively. The particle size of OP-loaded NPs and OP-loaded NPs targeted with SBP1 peptide were 162.0±11.0 and 226.9±21.4 nm, respectively. While the zeta potential of the produced OP-loaded NPs was achieved negatively −23.9±1.21 mV), the result of the modification with SBP1 peptide this value approached zero as −4.59±0.728 mV. Morphological features of the OP-loaded NPs were evaluated using FEG-SEM. The further characterization and surface modification of the NPs were analyzed by FT-IR. In-vitro release studies of NPs showed that sustained release of OP occurred for two months that fitting the Higuchi kinetic model. By evaluating these outputs, it was reported that surface modification of OP-loaded NPs was significantly effective on characteristics such as size, zeta potential values, surface functionality, and release behavior. The therapeutic model drug-loaded polymeric formulation targeted with a specific peptide may serve as an alternative to more effective and controlled release pharmaceuticals in the treatment of COVID-19 upon an extensive investigation.

Angiotensin(1-7)-Stearic Acid Conjugate: Synthesis and Characterization

“…Measurements were performed at 25 °C ± 1 °C with a material refraction index of 1.33, and viscosity of 0.8872 cp. All measurements were performed in triplicate (26).…”

“…Then the above-mentioned washing process was done again. These processes (deprotection, activation, and coupling) were continued until all amino acids were added (26). The N-terminal end of the peptide was acetylated by adding 0.5M acetic anhydride solution together with 0.125 M DIEA and 0.015 M HOBt.H2O in DMF.…”

Advances in Pathogenesis, Progression, Potential Targets and Targeted Therapeutic Strategies in SARS-CoV-2-Induced COVID-19

“…Unlike SARS-CoV-2-HRP2, which is designed on a single amino acid, [SARSHRC-PEG4]2-chol, as a dimeric lipopeptide has better membrane fusion inhibition and lower cytotoxicity against SARS-CoV-2 entry ( 108 ). After that, one study designed a peptide SBP1 composed of 23-mer peptides to prevent the virus from entering the host cell by disrupting the combination of SARS-CoV-2-RBD and ACE2 ( 109 ). To inhibit the combination of viral S protein and ACE2, a study designed two types of peptide inhibitors, AHB1/2 and LCB1/3, by two de novo synthesis approaches around the ACE2 helix structure and RBD motif, which have a strong SARS-CoV-2 neutralization effect with IC 50 values of 35/15.5 nmol/L and 23.54/48.1 pmol/L, respectively ( 110 ).…”

Potential Application of Bionanoparticles to Treat Severe Acute Respiratory Syndrome Coronavirus-2 Infection

“…It works in therapy after activating into carboxylate form. This drug was encapsulated into PLGA nanoparticles to develop an efficient and prolonged release antiviral drug delivery system (Ucar et al, 2021). This formulation development aimed to target the spike-binding peptide-1.…”