Chitosan nanoparticles as drug carrier of gentamicin - density functional theory and molecular dynamics simulation studies

To the best of our knowledge, the detailed evaluation of the interaction of gentamicin with chitosan nanoparticles in the absence and presence of Sodium bis(2ethylhexyl) sulfosuccinate (AOT) surfactant followed by the evaluation of structural, dynamical, and thermodynamic properties was carried out for the first time which helped to understand the relative drug retention and release time in the model drug delivery system. Gentamicin being an unstable drug molecule demonstrated low efficacy against brucellosis as well as considerable toxicity, thus requiring frequent dosing in different forms including a single dose and combination with other antibiotics; however, no satisfactory result was observed. Chitosan is biodegradable and biocompatible which could help overcome drug delivery issues enabling the drug to reach the target site. Our study is based on the investigation of the chitosan-drug systems without and with the surfactant for the evaluation of the structural, dynamical, and transport properties using a combined approach consisting of density functional theory (DFT) calculations and molecular dynamics (MD) simulations. The DFT results showed that increasing the size of the chain consisting of D-glucosamine facilitated its interaction with the drug molecule thus signifying the role of polymer for the drug accommodation. Furthermore, MD simulation results exhibited the interaction of chitosan nanoparticles with the drug molecules via H-bonding and hydrophobic contacts which were enhanced after the addition of the surfactant. The dynamics and thermodynamic data corroborated the structural properties of the drug-nanoparticle interaction which confirmed the perturbation of the simulation system after the addition of the surfactant. The investigation of another two simulation systems based on the polymer constituents, D-glucosamine pointed towards the significance of the polymerization which eventually resulted in nanoparticles thus providing a platform for drug adsorption. The gentamicin-chitosan nanoparticles were further characterized via transport properties in terms of drug diffusion coefficients which served to consider its use in the context of target drug delivery to treat brucellosis.