Quercetin (Q) dietary supplements exhibit poor oral bioavailability because of degradation throughout gastrointestinal digestion (GD), which may be overcome using mesoporous silica particles (MSPs) as an oral delivery system (ODS). This study aimed to elucidate the effect of the functionalization of MSPs with amine-(A-MSP), carboxyl-(C-MSP), or thiol-(T-MSP) groups on their efficiency as a quercetin ODS (QODS). The type and degree of functionalization (DF) were used as factors in an experimental design. The Q-loaded F-MSP (F-MSP/Q) was characterized by gas physisorption analysis, loading capacity (LC), and dynamic light scattering and kinetics of Q release at gastric and intestinal pHs. Antioxidant capacity and Q concentration of media containing F-MSP/Q were evaluated after simulated GD. A-MSP showed the highest LC (19.79 ± 2.42%). C-MSP showed the lowest particle size at pH 1.5 or 7.4 (≈200 nm). T-MSP exhibited the maximum Q release at pH 7.4 (11.43%). High DF of A-MSP increased Q retention, regardless of pH. A-MSP preserved antioxidant capacity of Q-released gastric media (58.95 ± 3.34%). Nonetheless, MSP and F-MSP did not protect antioxidant properties of Q released in intestinal conditions. C-MSP and T-MSP showed essential features for cellular uptake and Q release within cells that need to be assessed.
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