Abstract
An enzyme-responsive colon-specific delivery system was developed based on hollow mesoporous silica spheres (HMSS) to which biodegradable chitosan (CS) was attached via cleavable azo bonds (HMSS–N=N–CS). Doxorubicin (DOX) was encapsulated in a noncrystalline state in the hollow cavity and mesopores of HMSS with the high loading amount of 35.2%. In vitro drug release proved that HMSS–N=N–CS/DOX performed enzyme-responsive drug release. The grafted CS could increase the biocompatibility and stability and reduce the protein adsorption on HMSS. Gastrointestinal mucosa irritation and cell cytotoxicity results indicated the good biocompatibility of HMSS and HMSS–N=N–CS. Cellular uptake results indicated that the uptake of DOX was obviously increased after HMSS–N=N–CS/DOX was preincubated with a colonic enzyme mixture. HMSS–N=N–CS/DOX incubated with colon enzymes showed increased cytotoxicity, and its IC50 value was three times lower than that of HMSS–N=N–CS/DOX group without colon enzymes. The present work lays the foundation for subsequent research on mesoporous carriers for oral colon-specific drug delivery.
Highlights
Stimuli-responsive drug delivery systems (DDSs) have attracted extensive attention for the efficient loading and selective release of drugs in targeted diseased tissues [1]
After hollow mesoporous silica spheres (HMSS)–N=N–CS/DOX was preincubated with the colonic enzyme mixture for 1 h, the mean fluorescence intensity (MFI) markedly increased to 357 and even exceeded that of the free DOX group owing to the accelerated drug release from HMSS–N=N–CS/DOX after the breakage of azo bonds. All these results indicated that the azo bonds in HMSS–N=N–CS/DOX could be cleaved in the presence of colonic enzymes, which led to the shedding of CS from the surface of HMSS and accelerated the DOX release from HMSS
DOX was loaded in the hollow cavity and mesopores of HMSS in a noncrystalline state with a high loading efficiency of 35.2%
Summary
Stimuli-responsive drug delivery systems (DDSs) have attracted extensive attention for the efficient loading and selective release of drugs in targeted diseased tissues [1]. Oral DDSs meet a strong acidic environment in the stomach, which might accelerate the degradation of loaded drugs in the GI tract, removing the ability to realize colonic targeted delivery [19]. For this reason, several pH-dependent DDSs have been designed to realize pH-triggered drug release at the nearly neutral pH values (6–7) of the GI tract, resisting the highly acidic conditions in the stomach region [20–23]. A slight difference in acidity between the intestinal (pH 6.8) and colonic (pH 7.4) regions exists; such pH-responsive DDSs have difficulty realizing colonspecific release
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