Dual response to pH and chiral microenvironments for the release of a flurbiprofen-loaded chiral self-assembled mesoporous silica drug delivery system

This study examined the effects of pH and chirality on the release of flurbiprofen (FP)-loaded chiral (L/D) self-assembled mesoporous silica nanoparticles (CSA-L/D-MSNs), which were synthesized using cationic cetyltrimethyl ammonium bromide (CTAB) as a template and chiral modified using L/D-tartaric acids. The morphology and physicochemical properties of the CSA-L/D-MSNs were systemically determined and compared with those of non-functionalized mesoporous silica nanoparticles (MSN). The results showed that the CSA-L/D-MSNs were spherical nanoparticles, and the chirality in the L/D-tartaric acids was successfully imparted to the CSA-L/D-MSNs. FP could be loaded into the CSA-L/D-MSNs and was effectively transformed from the crystalline state to an amorphous state after drug loading due to the finite size effect. The release of FP@CSA-L/D-MSNs was faster than that of FP in a pH 1.2 medium and slower in a pH 6.8 medium, and it was better than that of FP@MSNs in both release mediums. Meanwhile, the FP@CSA-L/D-MSNs exhibited a clearly enhanced pH response because the negatively charged carboxyl groups on their surface induced stronger electrostatic repulsion between FP and CSA-L/D-MSNs. Moreover, the effect of the chiral environment on the release of FP@CSA-L/D-MSNs was further studied by introducing small-molecule chiral additives (L/D-alanine). It was found that the release of FP was inhibited in a chiral environment. Particularly, the CSA-L/D-MSNs began to exert the chiral recognition function, in which the CSA-L-MSN responded to chiral stimuli and enhanced the cumulative release amount from 84.25 %–89.11 % in a pH 6.8-L medium, while the CSA-D-MSN showed a suppressed release in the pH 6.8-L medium. Notably, the CSA-L/D-MSNs exhibited intelligent drug release by both chirality response and pH response, and will provide valuable guidance for the design of drug delivery systems.