Microscopic diffusion mechanism of linezolid in carbon-based nanoporous materials: a molecular dynamics simulation study

Introduction Graphene aerogels are promising antibiotic delivery carriers owing to their ultralow density, hierarchical porous architecture, and high specific surface area. However, molecular transport within their nanoscale confined spaces remains poorly understood, limiting the rational design of carriers with controllable release performance. This study investigated linezolid diffusion within graphene aerogel-like confined structures. Methods All-atom molecular dynamics simulations using the OPLS-AA force field were performed with a solvent-free model containing more than 10,000 atoms. Randomly overlapping graphene sheets were used to represent the disordered porous framework. A controlled-variable approach was adopted to quantify the independent effects of temperature (240–380 K), carrier dosage (20–150 graphene sheets), and drug loading (1,000–5,832 molecules) on diffusion coefficients. Grid-based pore-size analysis was used to examine the relationship between local pore geometry and molecular transport. Results Increasing temperature enhanced diffusion nonlinearly over the investigated range. At fixed drug loading, increasing carrier dosage enlarged the mean local pore size from 3.97 to 7.32 Å and increased the diffusion coefficient overall, reaching 3.120 × 1 0 ‐ 12 m 2 / s . Increasing drug loading shifted the calculated pore-size distribution toward smaller local voids, with the mean local pore size decreasing to 2.11 Å. Nevertheless, the highest drug-loading condition exhibited enhanced diffusion despite the smaller mean local pore size. An empirical power-law relationship between diffusion coefficient and mean local pore size was obtained for the carrier-dosage series; the high drug-loading systems were excluded from this fit. Discussion These findings suggest that pore geometry, molecular interactions, and the confined environment jointly influence linezolid transport, and that mean local pore size alone cannot explain diffusion under all loading conditions. The results provide microscopic insights and a preliminary structural reference for further studies of carbon-based drug carriers. Because the simulations excluded explicit solvents and ions, the reported diffusion coefficients should not be directly interpreted as values under physiological aqueous conditions.