High-capacity adsorption and pH-responsive release of an antihypertensive drug via urea- and cetyltrimethylammonium bromide-functionalized mesoporous carbons

Controlled drug delivery systems are increasingly investigated to optimize therapeutic efficacy and reduce the dosing frequency of antihypertensive agents such as losartan potassium. Ordered mesoporous carbons (OMCs), featuring uniform pore architecture, high loading capacity, and tunable surface chemistry, offer a versatile platform for the incorporation of drugs, while maintaining structural stability under physiological conditions. In this study, OMCs templated from KIT-6 were synthesized and functionalized with either urea or cetyltrimethylammonium bromide to enhance drug–carrier interactions. The functionalization route was modulated using different solvents to alter surface chemistry and partially preserve porosity. Structural and chemical characterization confirmed that solvent polarity influenced both the extent and location of modification: alcohols promoted internal grafting, whereas aqueous systems favored surface-level alteration. Functionalization significantly affected the pH responsiveness of the materials, shifting the zeta potential from consistently negative (pristine carbon) to a tunable range: slightly positive in acidic media, near-neutral at pH 7.2, and highly negative at basic pH. The highest adsorption capacity (280 mg/g) towards losartan potassium was achieved for carbon modified with urea in ethanol. At the same time, the greatest drug release (98.3 %) under near-neutral conditions occurred for the sample treated with surfactant in isopropanol. The thermodynamic analysis confirmed spontaneous physisorption across all materials, and release studies demonstrated clear pH-dependent desorption behavior. Cytotoxicity assays on Caco-2 and HIEC-2 cell lines further verified that the functionalized OMCs are non-toxic under biologically relevant conditions, underscoring their safety for oral administration. These findings support the use of surface-engineered mesoporous carbons as responsive drug carriers.