Abstract

Colorectal cancer is the third most common cancer in the world. Cromolyn is a mast cell stabilizer and was proposed as an anticancer agent; however its high polarity limits its bioavailability by rapid washing from the body. We formulated 10 cromolyn chitosan nanoparticles (CCSNPs)1 following ionic gelation technique to improve its bioavailability and investigated the protective anticancer effect of the optimum formula against colorectal cancer in dimethylhydrazine-induced model in rats. Rats were divided into seven groups, group-1: normal control, group-2: cromolyn control, group-3: CCSNPs control, groups-4 to 7 received dimethylhydrazine for 16 weeks to induce colorectal cancer. Groups-5 to 7 received cromolyn solution, non-medicated chitosan nanoparticles and CCSNPs, respectively as protective treatments. Optimum CCSNPs (size 112.4 nm, charge +39.9 mV, enclosed 93.6% cromolyn and showed a sustained drug release pattern over 48 h) significantly reduced tumor-signaling molecules and the number of aberrant crypt foci compared to dimethylhydrazine. Histopathological examination of colon samples revealed that CCSNPs exerted an augmented protective anticancer effect by ameliorating tumor pathology compared to cromolyn solution. In conclusion, CCSNPs ameliorated tumor pathology and malignant oncogenic signaling molecules in colorectal cancer tissue. Thus, CCSNPs may provide a novel protective approach in colorectal cancer treatment. Moreover, encapsulating cromolyn in chitosan nanoparticles augmented the protective anticancer effect of the drug.