One of the major challenges in medicine is the delivery and control of drug release over time. Current approaches take advantage of mesostructured silica nanoparticles (MSNs) as carriers but suffer several problems including complex synthesis that requires sequential steps for (1) removal of surfactants and (2) functionalization of MSNs to allow upload of the drugs. Here, a novel solution is presented to these restrictions: the design of drug-structure-directing agents (DSDAs) with dual inherent pharmacological activity and ability to direct the formation of solid and hollow-shell MSNs. Pharmacologically active DSDAs obtained by amidation of drugs with fatty acids are allowed to form micelles, around which the inorganic species self-assembled to form MSNs. Since the DSDAs direct the formation of MSNs, the steps to remove surfactants, functionalization, and drug upload are not required. The MSNs thus prepared provide sustained release of the drug over more than six months, as well as rapid cellular internalization by both physiological and tumoral human colon cells without affecting cell viability. Moreover, the gradual intracellular release of both, the active drug and lipid moiety with potential nutraceutical properties is proved. MSN particles designed with this approach are promising vehicles for controlled and sustained intra-or extracellular drug-delivery.

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We present here a detailed molecular-level understanding of the interactions among surface-functionalized mesoporous SBA-15 silica and pharmaceutical guests that influence macroscopic adsorption and release behaviors. A model drug species, methylprednisolone sodium succinate, was adsorbed on the surfaces of functionalized mesoporous SBA-15 silica materials with different aminoalkyl species and without or with C60 fullerene moieties. Zeta potential measurements show that the electrostatic interactions among methylprednisolone species and modified silica surfaces are important for the adsorption and release of the methylprednisolone molecules. Complementary one and two-dimensional (2D) solid-state 13C­{1H} NMR measurements provide evidence for specific intermolecular interactions between adsorbed methylprednisolone species and different types of functionalized silica surfaces. In particular, correlated 13C and 1H signal intensities from the methylprednisolone alkyl moieties and the aminoalkyl groups of the functionalized silica surfaces unambiguously establish their close (<1 nm) molecular proximities and strong interactions. The molecular-level insights are correlated with macroscopic adsorption and release behaviors of methylprednisolone, providing detailed new understanding of the interactions responsible for the high loadings and slow release of this important pharmaceutical agent from surface-functionalized mesoporous materials.