Chitosan capping enzyme-responsive hollow mesoporous silica nanoplatforms for colon specific drug delivery

Abstract In summary, an enzyme-responsive colon specific drug delivery system was developed based on hollow mesoporous silica sphere (HMSS), in which the biodegradable chitosan (CS) was gated on the openings of HMSS through cleavable azo bonds (HMSS-N=N-CS). Doxorubicin (DOX) was encapsulated into the hollow cavity and mesopores of HMSS, and HMSS-N=N-CS/DOX showed a high loading amount of 35.2%. X-ray diffraction (XRD) experiment proved that the DOX loaded in the HMSS-N=N-CS was in a non–crystalline state. In vitro drug release experiments proved that HMSS-N=N-CS/DOX showed an enzyme-responsive drug release property. The grafted CS could increase the biocompatibility and stability of HMSS, and reduce the protein adsorption on the surface of HMSS. The gastrointestinal mucosa irritation and cell cytotoxicity results indicated the good biocompatibility of HMSS and HMSS-N=N-CS. The confocal laser scanning microscope (CLSM) and flow cytometry technique (FCM) results indicated that the cellular uptake of DOX was obviously increased after the HMSS-N=N-CS/DOX was preincubated with colonic enzyme mixture. Cell viability result indicated that HMSS-N=N-CS/DOX incubated with colon enzyme showed an increased cytotoxicity and the IC50 value was three time less than that of HMSS-N=N-CS/DOX group. The present work will lay the foundation for subsequent research on mesoporous carriers for oral colon-specific drug delivery.