Rationally Designed Oral DOX Gels for Colon-Specific Administration

Abstract

Colorectal cancer (CRC) is the third leading cause of death from cancer in both men and women. Traditional CRC dosage forms deliver the drug to both desired and unwanted sites of drug action, resulting in a number of negative side effects. Chemotherapeutic and chemopreventive agents are being targeted and delivered directly to the colon and rectum using targeted oral drug delivery systems. The main challenge in successfully targeting drugs to the colon via the oral route is avoiding drug absorption/degradation in the stomach and small intestine before the dosage form reaches the colon. In this study, we employed biocompatible chalk to adsorb DOX, then mixed pectin and cross-linked with calcium ions to form PC–DOX gels. The presence of cross-linked pectin and chalk can provide dual protection for the drug, significantly reducing drug leakage in gastric acid. In vitro release results showed that the designed PC–DOX could achieve 68% colon delivery efficiency. In the simulated colon environment, the released semi-degradable chalk did not affect the uptake of doxorubicin by colon cancer cells. Finally, in vivo simulation experiments in mice showed that rationally designed PC–DOX could achieve the highest colonic delivery efficiency. Our strategy has great potential for application in the treatment of colon cancer.