Chitosan modified metal–organic frameworks as a promising carrier for oral drug delivery

Metal–organic frameworks (MOFs) are composed of both organic linkers and metallic ions, which have emerged as excellent drug delivery agents for the treatment of cancer and other diseases. Currently, MOF studies are mainly focused on intravenous administration, while studies dedicated to oral administration are relatively scarce. In this study, five MOFs, namely UiO-66, UiO-66-NH(2), UiO-66-COOH, UiO-67 and Zr-NDC, were synthesized, of which Zr-NDC had the largest drug loading capacity for 5-FU. Next, a chitosan (CS) modified Zr-NDC was developed to provide a strong impetus for the oral administration of 5-FU. In vitro release experiments of fluorescein isothiocyanate (FITC)-labeled chitosan demonstrated that the cumulative release rates of FITC-labeled chitosan in artificial gastric juice and artificial intestinal fluid were about 20% and 90%, respectively. The in vitro drug release profiles showed that under the protection of CS-MOF, the release of 5-FU into an acidic environment was only 20%, but the release in artificial intestinal fluid reached 70%. Pharmacokinetic analysis revealed that the coating of chitosan on the surface of MOFs exerted a controlled drug release effect, and further improved the oral bioavailability of 5-FU. These findings suggest that CS coating can break through the limitation of MOF intolerance to acid. It is expected that CS-MOF@5-FU can serve as a potential drug delivery system for the oral administration of 5-FU.