Two-Level Adsorption of Ibuprofen on C₆₀ Fullerene for Transdermal Delivery: Classical Molecular Dynamics and Density Functional Theory Computations

Abstract

We have investigated the nonsteroidal anti-inflammatory drug ibuprofen (IBP) adsorbed noncovalently on buckminsterfullerene C 60 for its transdermal delivery through computational simulations using classical molecular dynamics and density functional theory (DFT). Following geometry optimization procedures, it is shown that IBP assumes two distinct adsorption geometries (A and B) with binding energies which allow both structures to be stable at room temperature, giving rise to a two-level adsorption and, possibly, to an extended anti-inflammatory delivery time. The electron transfer between IBP and C 60 was estimated, showing that IBP acquires a small amount of negative charge which is concentrated at the isobutyl group. The electronic structure results suggest that the IBP adsorption on C 60 can be probed by performing light absorption and luminescence measurements but not the existence of the two-level adsorption since the calculated HOMO–LUMO energy gaps for the A and B IBP@C 60 adsorbates are very close, by about 2.7 eV. A classical molecular dynamics simulation for 60 IBP molecules interacting with a single buckyball at 300 K shows three solvation layers, where the IBP molecules assume geometries which are close to A IBP@C 60 in the most internal layer and to B IBP@C 60 in the two external layers, confirming the two-level adsorption. A vibrational analysis was also carried out for adsorbed IBP, showing that the IR absorption spectrum of A is very similar to B. The largest frequency mismatch between the two adsorption geometries occurs for two modes below 600 cm –1 . The Raman spectra for both A and B are dominated by C 60 normal modes.