Colistin (polymyxin E) is an effective antibiotic against Gram-negative bacteria, but its clinical use is limited due to its high toxicity. Targeted drug delivery, which has made significant progress in reducing drug toxicity in recent years, could be an ideal approach to mitigate the nephrotoxicity and neurotoxicity associated with this drug. However, the complexity of drug design and manufacturing remains a major challenge in the pharmaceutical industry. To address this, we investigated polymeric drug delivery systems for colistin encapsulation using molecular dynamics simulations. In this study, the MARTINI 3 force field within GROMACS 2022 software was employed to model and simulate various systems, including unmodified hyaluronic acid (HA), HA modified with two and four hydrophobic groups, and a combination of polyvinyl alcohol (PVA) and polystyrene sulfonate (PSS). Structural analysis of the systems was performed based on indices such as root-mean-square deviation (RMSD), radius of gyration (Rg), radial distribution function (RDF), and solvent-accessible surface area (SASA). The results indicated that hydrophobic modification of HA increased aggregation, reduced the radius of gyration, and enhanced the system's stability in the presence of colistin. Among the modified systems, HA with four hydrophobic groups (HA(4)) exhibited the highest structural stability. Additionally, the PVA-PSS polyelectrolyte complex displayed stable behavior, formed a bilayer structure, and demonstrated effective interactions with the drug. Targeted chemical modifications and the use of hybrid polymers can facilitate the design of stable, efficient, and controllable systems for colistin delivery. This study provides a viable pathway for the development of safe nanocarriers with high encapsulation efficiency under realistic conditions.
Azadi et al. (Thu,) studied this question.