A safe, localized treatment for chronic inflammation in the intestinal tract will move one step closer to helping patients reduce their risk of developing colon cancer, thanks to a three-year, $433,000 National Institutes of Health grant awarded to professor Hemachand Tummala of the Department of Pharmaceutical Sciences.
Current treatments for inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, can have deadly side effects and inconsistent results. Therefore, Tummala said, “there is an urgent need for safer, targeted therapeutics that deposit the medication in the intestinal tract.” He and his research group developed a patented formulation that releases the anti-inflammatory power of curcumin in the colon, reducing inflammation and even healing sores or ulcers during proof-of-concept testing in mouse models.
Through the NIH grant, Tummala will continue working with Dr. Amar B. Singh, a gastrointestinal biochemist and professor at the University of Nebraska Medical Center and a researcher at the Fred & Pamela Buffett Cancer Center in Omaha, to perform preclinical testing on the specialized formulation, known as Ora-Curcumin S. The researchers will evaluate the formulation’s effectiveness in multiple mouse models of inflammatory bowel disease. SDSU will receive about $260,000 through the NIH project.
“In my conversations with the clinicians who have firsthand experience with IBD patients, I have found that the use of curcumin for these patients is considered very good. My partnership with Dr. Tummala is taking the right step towards realizing this ‘bench-to-bedside’ goal. I am excited about the forward-going prospective of our collaboration,” Singh said.
Colon cancer is the second-leading cause of cancer deaths among American men and women combined, according to the Centers for Disease Control and Prevention. Furthermore, colorectal cancer is now the leading cause of cancer death among Americans under age 50, according to the NIH National Cancer Institute. Half of these young adults with colorectal cancer have a chronic condition that can cause inflammation of the gut.
Most patients with inflammatory bowel diseases are diagnosed in their 20s and 30s, according to CDC statistics. Therefore, developing effective ways to reduce or manage inflammation could be life-changing
Unleashing anti-inflammatory power of curcumin
Curcumin is the main component in turmeric, the yellow spice that flavors Indian curry and is a safe, potent natural anti-inflammatory, Tummala explained. However, accessing the anti-inflammatory benefits of curcumin is difficult because it does not dissolve in water, therefore the body cannot absorb it.
Using Food and Drug Administration-tested polymers, Tummala, and his research group were able to make curcumin 2,000 to 3,000 times more soluble and stable in water. In addition, the formulation dissolves only when it reaches the later parts of the intestine including colon. They call this novel formulation Ora-Curcumin S.
“The formulation does not let any curcumin into the blood and releases it only in the lumen of the colon for localized treatment, he said.
Through thorough preliminary studies, Tummala and Singh found healthy mice that began receiving the Ora-Curcumin S formulation two days before being subjected to a chemical that causes symptoms, such as ulcers, bleeding and diarrhea, similar to those of ulcerative colitis patients, had less colon damage and inflammation. Results were published in the Journal of Controlled Release.
Further testing through a $14,537 SDSU Research, Scholarship and Creative Activity Challenge Fund grant helped Tummala strengthen the NIH grant proposal.
The formulation worked on healthy mice, but that did not provide an accurate representation of a patient, Tummala explained. Therefore, he and Singh tested the curcumin formulation on mice with ulcerative colitis. They saw the curcumin formulation actually attached to the sores or ulcers in the inflamed colons.
“When the formulation dissolves, the polymer sticks to or coats the ulcers,” Tummala said. “It’s like applying an ointment in the colon.”
In addition, the researchers compared the effects of unformulated curcumin and Ora-Curcumin S at lower dosages than the original proof-of-concept study. “We found dosages (of Ora-Curcumin S) three to 10 times lower than what others have previously reported for curcumin to be effective,” he said. “These experiments enhanced our grant potential and the investment reaped major benefits.”
Another major goal of the grant is to enhance research exposure and training for students from South Dakota. Two Ph.D. students and multiple undergraduates will work on the project receiving training in the biomedical and drug discovery research.
Tummala concluded, “This NIH project will not only establish a pathway, for the first time, for clinical testing of this local therapy of curcumin, but also advance a novel inflammation-targeted delivery technology for other drugs to treat inflammatory bowel disease.