Design and synthesis of functionalized cellulose nanocrystals-based drug conjugates for colon-targeted drug delivery

Abstract

With excellent biological, physical and chemical properties of cellulose nanocrystals, a novel colon-targeted drug release system was created by conjugating of model drug (tosufloxacintosilate, TFLX) with maleic anhydride cellulose nanocrystals (MCNCs), in which l-leucine was used as a spacer molecule. The satisfactory drug loading of 29.14% as well as high encapsulation efficiency of 99.84% were obtained. The hydrodynamic diameters of MCNCs, drug (TFLX) and drug conjugates are 124, 491 and 520 nm, respectively, which demonstrates that MCNCs might adhere to the surface of drug tightly. The successful linking of l-leucine to MCNCs and amidation reaction between drug and A-MCNCs were confirmed by FTIR and XPS spectra. Moreover, the release behaviors of drug conjugates and fluorescent-labeled drug conjugates in simulated fluids were investigated by in vitro study and fluorescence detection. It is found that the drug conjugates could release about 72.55% of the drug loaded in the simulated colon fluid with enzyme lysozyme after 30 h, but no drug was detected in simulated gastric fluids with enzyme pepsin. The results illustrate that the model drug could be entrapped efficiently by MCNCs and have an excellent behavior for colon-targeted release. The paper reveals that cellulose nanocrystals can be considered potential carriers in colon specific drug delivery system.