Calcium carbonate hollow microspheres encapsulated cellulose nanofiber/sodium alginate hydrogels as a sequential delivery system

By using folic acid (FA) as the template, calcium carbonate hollow microspheres (CaCO 3 HMs) are prepared through the Ostwald ripening process, which can be utilized for the loading of doxorubicin hydrochloride (DOX). The DOX loaded CaCO 3 HMs (CaCO 3 /DOX) are co-encapsulated with ibuprofen (IBU) in the cellulose nanofiber (CNF)/sodium alginate (SA) hydrogels cross-linked by Ca 2+ . The loading efficiency of DOX in the CaCO 3 HMs is 95.7 %, and the loading efficiency of IBU in the hydrogels is 97.0 %. In the weakly alkaline environment (pH ~7.4) that is characteristic of intestinal fluids of human body, the CNF/SA hydrogels are swollen and the encapsulated IBU is first released for pain control, and the release rate of IBU can reach 57.8 %. In the weakly acidic environment (pH ~6.5) that is characteristic of colonic fluids of human body, the CaCO 3 HMs are decomposed to release the loaded DOX with a release rate of 50.1 %, which can be used for the treatment of colorectal cancer. The results of release kinetics indicate that the delivery of IBU is governed by first-order model and DOX by zero-order model. The developed sequential delivery system (SDS) can not only enable the release of DOX in colon of human body, but also simultaneously relieve the pain of patients during the chemotherapy of colon cancer.