Polysaccharide, fecal microbiota, and curcumin-based novel oral colon-targeted solid self-nanoemulsifying delivery system: formulation, characterization, and in-vitro anticancer evaluation

Abstract

The use of polysaccharides in preparation of microbially triggered colon-targeted delivery system has been explored extensively to deliver drugs at the colonic site. This type of targeting is attributed to inherent property of polysaccharides by virtue of which they are digested in the gut only by the colonic microflora. In last two decades, the use of fecal microbiota transplantation (FMT) has been reported widely to treat colonic diseases such as Crohn's disease, irritable bowel syndrome, and recurrent Clostridium difficile infection. It has been established that FMT downregulates inflammatory proliferation and pro carcinogenic pathways. Although a few reports exist on the use of colon-targeted FMT capsules in increasing the microbial diversity of gut microflora, they have not been able to establish clinical superiority of the colon-targeted capsules over conventional orally administered capsules. Hence, in the present study, an attempt has been made to utilize a multipronged strategy through a single formulation, wherein an anticancer phytoconstituent, polysaccharides, fecal microbiota extract (FME), and nanodelivery systems have been designed for the effective treatment of colon cancer. Overall, the study is aimed toward the development of an oral colon-targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) in which curcumin (CCM) was loaded. These SNEDDS were added to polysaccharide mixture of guar gum, pectin, lactose along with aerosol 200 (A-200) and then to the slurry of fecal microbiota extract. The liquid was then freeze dried and developed into solid SNEDDS powder. The process of formulating liquid SNEDDS was optimized using ternary phase diagram and Box Behnken Design. The developed formulation was characterized for physicochemical, physicomechanical, drug release and cytotoxic potential studies. The droplet size of reconstituted S-SNEDDS was found to be 78.46 ± 0.87 nm. The site-specific release of S-SNEDDS powder was confirmed by dissolution studies in medium containing rat caecal contents, wherein, the formulation containing guar gum and pectin in 1% w/w ratio showed less than 10% drug release in initial 5 h and burst release between 5th and 10th h indicating colon-specific release of CCM. Significant cytotoxic effect was seen for CCM-loaded S-SNEDDS as compared to control formulations. The use of 16s metagenomic technique confirmed no significant change in fecal microbiota composition of formulation pre- and postlyophilization. Overall, the study suggested a novel, oral colon-targeted SNEDDS-based formulation containing fecal microbiota and CCM for the treatment of colon cancer.