Comparative In-Silico Evaluation of 4′-Fluorouridine and Favipiravir Pulmonary Delivery via PEGylated Graphene Oxide Nanocarriers

Oluwasegun Chijioke Adekoya¹, Gbolahan Joseph Adekoya¹, Yskandar Hamam^2,3 & Emmanuel Rotimi Sadiku¹

¹Institute of Nanoengineering Research, Department of Chemical, Metallurgical and Materials Engineering, Faculty of Engineering and the Built Environment, Tshwane University of Technology, Pretoria 0001, South Africa

²Department of Electrical Engineering, Faculty of Engineering, and the Built Environment, Tshwane University of Technology, Pretoria 0183, South Africa

³École Supérieure d’Ingénieurs en Électrotechnique et Électronique, Cité Descartes, 2 Boulevard Blaise Pascal, Noisy-le-Grand, Paris 93160, France

Summary

This study presents a comparative in-silico evaluation of 4′-Fluorouridine (4′-FlU) and Favipiravir (FAV) pulmonary delivery using PEGylated graphene oxide (GO/PEG) nanocarriers. Previously, ab initio simulations of 4′-FlU [1] and FAV [2] were reported independently. Here, these datasets are integrated for the first time into a direct benchmarking analysis, enabling systematic comparison of adsorption dynamics, charge transfer, thermodynamic stability, and release kinetics under gas, aqueous, acidic, and alkaline environments. The GO/PEG–4′-FlU complex exhibited moderate adsorption energies (−33.72 to −118.42 kcal/mol) and phase-responsive release kinetics (τ ≈ 4.94 × 10¹¹ ms in aqueous phase), consistent with controlled pulmonary delivery [7]. By contrast, FAV displayed excessive binding affinity in acidic environments (−179.11 kcal/mol), leading to impractically long release times (τ ≈ 1.48 × 10¹¹¹ ms). Both complexes showed spontaneous and exothermic interactions (ΔG < 0, ΔH < 0), but only 4′-FlU exhibited favourable miscibility in acidic phases (χ = −208.91), supporting superior dispersion in inflamed pulmonary tissues. By placing these published datasets in direct comparison, this analysis highlights the relative advantages of 4′-FlU for phase-responsive nanocarrier delivery, while identifying limitations of FAV in acidic microenvironments. The comparative framework introduced here provides a transferable methodology for evaluating antiviral candidates and informs the rational design of nanocarriers for inhalation therapy.