Predictive Modelling of 6-Fluoro-3-Hydroxy-2-Pyrazine Carboxamide Drug Delivery Efficacy in Pegylated Bionanocomposite Through First Principles Simulation

Abstract This research investigates the drug delivery efficacy for 6-fluoro-3-hydroxy-2-pyrazinecarboxamide (Favipiravir) in PEGylated bionanocomposites using a predictive modelling approach. The study focuses on understanding the interaction mechanisms between Favipiravir (FAV) and polyethylene glycol (PEG)/graphene oxide (GO) (GO/PEG) nanosheets, across various environmental conditions. To evaluate drug delivery efficacy, the following key parameters were calculated: adsorption energies ranging from-202.61 to -3.46 kcal/mol indicating the strength of binding between the drug and nanocarrier; net charge transfer values between -0.222 to 0.373 electrons, reflecting the degree of charge migration; release times spanning a wide range from 3.4×10⁻¹⁴ to 2.38×10¹³² ms, which impacts the drug release kinetics; and thermodynamic parameters such as changes in Gibbs free energy (ΔG) between 183.34 and 16.95 kcal/mol, and changes in enthalpy (ΔH) between -203.64 and 0.55 kcal/mol, providing insights into the favorability and spontaneity of the drug-nanocarrier interactions. The results show that incorporating PEG onto GO nanosheets enhances adsorption energies and binding affinities for Favipiravir. Environmental factors and PEGylation influence the charge transfer and non-covalent interactions. PEGylation leads to faster Favipiravir release kinetics. Favorable thermodynamics are observed, especially in aqueous environments. Electronic properties, quantum descriptors, and theoretical spectra provide further insights into molecular interactions.