Multi-unit pellet drug delivery system of Danggui Decoction extracts for chemoprevention of IBD-associated colorectal cancer in rats

Abstract

Anti-inflammation has become pivotal in chemoprevention of inflammatory bowel disease (IBD)-associated colorectal cancer (CRC). The chemopreventive effects of anti-inflammatory drugs currently used in IBD therapy are still not clear based on existing epidemiological studies. Therefore, novel chemopreventive candidates need to be investigated and natural products derived from food as well as complementary and alternative medicine have become attractive resources with advantages including multi-components and multi-targets. Danggui Decoction (DGD), composed of Angelicae Sinensis Radix, Zingiberis Recens Rhizoma and Jujubae Fructus, is a traditional Chinese medicinal formula for the treatment of IBD, and DGD supercritical fluid extracts (DGDSFE) as well as DGD polysaccharide extracts (DGDPE) are potential effective constituents for chemoprevention. This article constructed a multi-unit pellet drug delivery system (MUPDDS) containing two independent parts, DGDSFE colon-targeted pellets and DGDPE pellets, according to the different characteristics of extracts, by applying extrusion-spheronization and coating technology. The chemopreventive effect of this MUPDDS was evaluated in the rat model induced by 1,2-dimethylhydrazine and dextran sulfate sodium. The tumor incidence, tumor number and tumor volume were reduced after the administration of MUPDDS daily for 14 weeks, with serum levels of TNF-α, IL-1β and hepcidin decreased and levels of IFN-γ and IL-2 in splenocyte supernatant elevated, indicating anti-inflammation, iron metabolism regulation and immune regulation of DGDSFE and DGDPE in MUPDDS. Furthermore, the feasibility and advantage of MUPDDS in chemoprevention was displayed by compared with extracts, DGDSFE colon-targeted pellets or DGDPE pellets, providing an inspiring strategy to achieve better effect of traditional Chinese medicines in cancer prevention.