Bridging experiment and molecular dynamics: Mefenamic acid confinement in nanocrystalline cellulose aerogels under scCO2 conditions

Surfaces and Interfaces. 2026. Vol. 98. Article 110545.

D.L. Gurina, Fashchevsky K. A., Oparin R. D., Dyshin A. A., Yu.A. Budkov, Kiselev M. G.

In this work, we combine experimental characterization and molecular dynamics (MD) simulations to elucidate the molecular mechanisms governing the impregnation of mefenamic acid (MFA) into nanocrystalline cellulose (NCC) aerogels. NCC aerogels were impregnated with MFA in scCO2, and low-temperature nitrogen adsorption revealed a concentration-dependent decrease in surface area, pore volume, and pore size, with an increase in pore volume in the 3–4 nm range after washing the highly loaded sample, suggesting permanent deformation of sub-2 nm pores caused by disjoining pressure. MD simulations of NCC slit pores (1.7 and 3 nm) and a non-frozen aerogel model provided molecular-level insight into pore-size-dependent adsorption dynamics. The simulations revealed a sequential filling process involving initial adsorption on the external surface, followed by occupation of the internal pore surface. Moreover, the time required to reach adsorption equilibrium exhibited opposite concentration dependences in narrow and wide pores. Hydrogen bonding analysis revealed that at low concentrations, MFA primarily forms bonds with cellulose; upon saturation, MFA-MFA hydrogen bonds become dominant. Disjoining pressure calculations showed that confined MFA generates substantial mechanical stresses in the narrow pore, significantly exceeding those of pure scCO2, while stress in the wider pore remains low. Simulations of a non‑frozen aerogel further demonstrated pronounced swelling with increasing MFA concentration. This integrated approach provides a molecular understanding of drug impregnation into cellulose aerogels, highlighting the roles of surface saturation, hydrogen bonding, and disjoining pressure in determining loading efficiency and pore morphology.

Keywords: сверхкритические флюиды, Supercritical fluids, классическая молекулярная динамика, Impregnation, Импрегнация, classical molecular dynamics, aerogels, аэрогели