Predictive Modeling 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 modeling 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 and 0.373 electrons, reflecting the degree of charge migration; release times spanning a wide range from 3.4 × 10 −14 to 2.38 × 10 132 ms, which impacts the drug release kinetics; and thermodynamic parameters such as changes in Gibbs free energy (Δ G ) between 183.34 and 16.95 kcal/mol, and changes in enthalpy (Δ H ) 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 FAV. Environmental factors and PEGylation influence the charge transfer and noncovalent interactions. PEGylation leads to faster FAV release kinetics. Favorable thermodynamics are observed, especially in aqueous environments. Electronic properties, quantum descriptors, and theoretical spectra provide further insights into molecular interactions.