Thesis (M.Sc) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

Colorectal cancer (CRC) 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. Ten different formulas of cromolyn chitosan nanoparticles (CS NPs) were formulated following ionic gelation technique to improve cromolyn bioavailability. The protective anticancer effect of the optimum formula (F6: size 112.4 nm, charge +39.9 mV, enclosed 93.6% cromolyn and showed a sustained release pattern over 48 hr) were investigated in experimentally-induced CRC rats using dimethylhydrazine (DMH) for 16 weeks. Rats were divided into seven groups, Group 1: Normal control, Group 2: Cromolyn control, Group 3: Cromolyn CS NPs control, Groups 4 to 7 received DMH for 16 weeks to induce CRC. Groups 5 to 7 received cromolyn solution, non-medicated CS NPs and cromolyn CS NPs, respectively as protective treatments. Cromolyn CS NPs significantly reduced colon Akt, Bcl-2, Ý-catenin, GSK-MAP Kinase, NF-{u049B}B P65, and S100P and MDA levels as well as decreased number of aberrant crypt foci compared to DMH group, whereas cromolyn solution decreased colon MDA level only without affecting the other studied parameters. Histopathological examination of colon samples revealed that cromolyn CS NPs exerted an augmented protective anticancer effect by ameliorating tumor pathology compared to cromolyn solution

Issued also as CD