INTRODUCTION: Effective treatments for human colorectal cancer, the second leading cause of cancer-related deaths, are urgently needed. Suppositories are commonly prescribed as palliative therapy for colorectal cancer patients undergoing radiation; however, use of this dosage form for eradicating tumors in the colon may offer an additional clinical option. We report on the development of different suppositories for this purpose. OBJECTIVE: We evaluated in vitro the cytotoxic effects of doxorubicin hydrochloride (DOX) against three human colorectal cancer cell lines. We next prepared three different suppository preparations, loaded with similar concentrations of doxorubicin and evaluated dissolution profiles, their general appearance, and storage capabilities. METHODS: Cytotoxicity assays were performed by Sulforhodamine B assay for three human colorectal cancer cell lines: Colo-205, HCT116, and LS174T. Suppository bases were PEG1500/4000 combination, PEG4000 and cocoa butter. Suppositories underwent stability testing via a dissolution apparatus set at physiological temperatures and in rectal pH environment of 7. RESULTS: Based on the cytotoxicity assays Colo-205 was most susceptible to the effects of DOX, followed by LS174T and HCT116. Of the three suppository base formulations, PEG 1500/4000 combination had the best dissolution profile. The suppository was able to dissolve in under 20 minutes and maintained an elegant appearance at 4 degrees for extended periods. CONCLUSIONS: Suppositories loaded with DOX have been demonstrated to be cytotoxic to colorectal cancer cells, and our studies support PEG 1500/4000 as a suppository base for future testing. Future studies in vivo will determine whether our novel suppository dosage form is more effective than DOX administered intravenously.
colorectal cancer, suppository, colon cancer, cancer treatment, doxorubicin
Fang, Elizabeth A., "Development and characterization of a novel suppository dosage form against human colorectal carcinoma" (2007). Honors Junior/Senior Projects. Paper 12. http://hdl.handle.net/2047/d10006539
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