Quantum DFT studies on the drug delivery of favipiravir using pristine and functionalized chitosan nanoparticles

Abstract

Considering the spread of the COVID-19 pandemic, finding new drugs along with the development of effective drug delivery methods can help in the treatment of this disease. For this reason, in this research work, the possibility of drug-delivery of Favipiravir (FP), one of the drugs approved in the treatment of COVID-19, by pristine chitosan (Chit) nanoparticles (NP), and functionalized chitosan nanoparticles with N-acylate, N-methyl, O-acetyl, and Oxazoline functional groups was studied using quantum mechanical DFT methods at B3LYP-D3(BJ)/6-311 + g(d,p) theoretical level in water medium. The QTAIM, NBO, DOS, frontier orbital, conceptual-DFT indices, and non-covalent interaction analysis were further implemented to investigate the possible interactions between FP and Chit NPs. The results show that the adsorption of FP on Chit NPs is done through the creation of hydrogen bonds, and the highest absorption energy of - 18.15 kcal/mol between pristine chitosan and FP. In the case of all functionalized Chit NPs, a decrease in the absorption energy is observed, which is more noticeable in the case of N-acylated and O-acetyl functionalize Chit NPs, and indicates the weakening of the van der Waals interactions for these cases. Considering the compatibility of Chit NPs with the human body and their non-toxicity, as well as the fact that factors such as pH, solubility, the ionic strength, and so on can be adjusted to control the release rate using the functionalized Chit NPs, it seems that the results of this work can be a comprehensive guide to design the drug delivery methods of FP drug using Chit NPs, to reduce the symptoms of COVID-19 disease.

Figure 1

Electrostatic potential energy surface (ESP) of optimized Chitosan nanoparticles and Favipiravir molecule. The red and blue points represent the local minima and maxima points of the ESP surface, respectively.

Figure 2

The electrostatic potential energy surface (ESP) for the optimized structures of (a) O-acetyl, (b) N-methyl, (c) N-acylate, and (d) Oxo- functionalized chitosan nanoparticles. The red and blue points represent the local minima and maxima points of the ESP surface, respectively.

Figure 3

Optimized structure of the functionalized chitosan nanoparticles and Favipiravir complexes, along with the bond-paths (magenta lines) representing the possible bonding interactions. The bond paths were calculated from the Bader’s QTAIM analysis.

Figure 4

Adsorption energy (E_ad) as a function of the distance between Chit and FP for pristine T11, T12, and T14 Chit/FP complexes.

Figure 5

Adsorption energy (E_ad) as a function of the distance between nanoparticle and FP for functionalized-Chit/FP complexes.

Figure 6

RDG plots of different Chit/FP complexes. The colorbar represents sign(λ)ρ(r) in atomic units.

Figure 7

Density of states (DOS) spectra of the studied Chit/FP complexes. In all cases, blue, red, and green lines are the TDOS, PDOS(Chit), and PDOS(FP), respectively.

Figure 8

Frontier HOMO and LUMO molecular orbitals of FP molecule, Chit nanoparticles, as well as T11, T12, and T14 Chit/FP complexes.

Figure 9

Frontier HOMO and LUMO molecular orbitals of functionalized Chit/FP complexes.