Molecular Characterization of Mesoporous Silica (Un)loading by Gemcitabine and Ibuprofen – An Interplay of Salt-Bridges and Hydrogen Bonds

The molecular mechanisms of mesoporous silica nanomaterial (MSN) loading by gemcitabine and ibuprofen molecules, respectively, are elucidated as functions of pore geometry. Based on a small series of MSN archetypes, we use molecular dynamics simulations to systematically explore molecule-by-molecule loading of the carrier material. Apart from predicting the maximum active pharmaceutical ingredient (API) loading capacity, more detailed statistical analysis of the incorporation energy reveals dedicated profiles stemming from the interplay of guest-MSN salt-bridges/hydrogen bonding in concave and convex domains of the silica surfaces - which outcompete interactions among the drug molecules. Only after full coverage of the silica surface, we find secondary layer growth stabilized by guest-guest interactions exclusively. Based on molecular models, we thus outline a two-step type profile for drug release from MSN networks. Subject to the MSN structure, we find 50–75 % of the API within amorphous domains in the inner regions of the pores – from which drug release is provided at constant dissociation energy. In turn, the remaining 50–25 % of drug molecules are drastically hindered from dissociation.