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Pharmacy researcher harnesses power of curcumin

By: Christie Delfanian
August 27, 2018

“Milk is an emulsion containing oil droplets dispersed in water,” explained Tummala, now an associate professor of pharmaceutical sciences at South Dakota State University. “Adding turmeric to boiling milk has a scientific reason besides centuries of success”.

Furthermore, he explained, “the main component of turmeric is curcumin, which is water insoluble. By boiling in milk, it will partition into oil droplets of milk. When we drink the turmeric milk, curcumin, a strong anti-inflammatory compound, gets into the blood along with fats.” Piperine, the active ingredient in black pepper, also increases the absorption of the curcumin.

“Grandma did not know this. This has been a traditional medicine for thousands of years because it works—and now we know why it is working,” said Tummala. “This is where the history became science.” He hopes to convert this science into medicine to help patients with inflammatory and neurological diseases, as well as cancer.

SDSU student honored for work with polymers

By: Dave Graves
September 27, 2017

A doctoral student at South Dakota State University has been honored with the 2016 Eudragit® Award for the North America region for his work on a patented product created at the campus lab.

Siddharth Kesharwani, a fourth-year pharmaceutical science doctoral student from India was honored Sept. 19 by Evonik Industries for innovative work involving Eudragit polymers.

Kesharwani and his supervisor, associate professor Hemachand Tummala, have been working on an orally bioavailable curcumin formulation. The novel curcumin formulation was developed using Eudragit polymers, which are manufactured by Evonik industries. A U.S. patent was recently issued to Tummala and his group for this novel formulation

ABSTRACT

Inflammatory Bowel Diseases (IBD) is a debilitating condition that affects ~70,000 new people every year and has been described as “an expensive disease with no known cure”. In addition, IBD increases the risk of developing colon cancer. The current therapeutics for IBD focus on the established disease where the immune dysfunction and bowel damage have already occurred but do not prevent or delay the progression. The current work de- scribes a polymer-based anti-inflammatory technology (Ora-Curcumin-S) specifically targeted to the luminal side of the colon for preventing and/or treating IBD. Ora-Curcumin-S was prepared by molecular complexation of curcumin with a hydrophilic polymer Eudragit® S100 using co-precipitation method. Curcumin interacted with the polymer non-covalently and existed in an amorphous state as demonstrated by various physicochemical techniques. Ora-Curcumin-S is a polymer-drug complex, which is different than solid dispersions in that the interactions are retained even after dissolving in aqueous buffers. Ora-Curcumin-S was > 1000 times water soluble than curcumin and importantly, the enhanced solubility was pH-dependent, which was observed only at pHs above 6.8. In addition, around 90% of Ora-Curcumin-S was stable in phosphate buffer, pH 7.4 and simulated intestinal fluid after 24h, in contrast to 10–20% unformulated curcumin. Ora-Curcumin-S inhibited Monophosphoryl Lipid-A and E. coli induced inflammatory responses in dendritic cells and cells over expressing Toll-Like Receptor-4 (TLR-4) suggesting that Ora-Curcumin-S is a novel polymer-based TLR-4 antagonist. Preliminary pharmacokinetics in mice showed targeted delivery of soluble curcumin to the colon lumen without exposing to the systemic circulation. Furthermore, Ora-Curcumin-S significantly prevented colitis and associated injury in a mouse model of ulcerative colitis estimated using multiple preclinical parameters: colonoscopy pictures, body weight, colon length, colon edema, spleen weight, pro-inflammatory signaling and independent pathological scoring. Overall, the outcome of this innovative proof-of-concept study provides an exciting and locally-targeted pathway for a dietary therapeutic option for IBD patients to help limit colonic inflammation and thus susceptibility to colitis-associated colorectal cancer.

ABSTRACT

Curcumin is a natural dietary compound with demonstrated potential in preventing/treating several chronic diseases in animal models. However, this success is yet to be translated to humans mainly because of its poor oral bioavailability caused by extremely low water solubility. This manuscript demonstrates that water insoluble curcumin (~ 1 ug/ml) forms highly aqueous soluble complexes (>2mg/ml) with a safe pH sensitive polymer, poly(butyl-methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl-methacrylate) when precipitated together in water. The complexation process was optimized to enhance curcumin loading by varying several formulation factors. Acetone as a solvent and polyvinyl alcohol as a stabilizer with 1:2 ratio of drug to polymer yielded complexes with relatively high loading (~ 280 ug/ml) and enhanced solubility (>2 mg/ml). The complexes were amorphous in solid and were soluble only in buffers with pHs less than 5.0. Hydrogen bond formation and hydrophobic interactions between curcumin and the polymer were recorded by infrared spectroscopy and nuclear magnetic resonance spectroscopy, respectively. Molecular complexes of curcumin were more stable at various pHs compared to unformulated curcumin. In mice, these complexes increased peak plasma concentration of curcumin by 6 times and oral bioavailability by ~20 times. This is a simple, economic and safer strategy of enhancing the oral bioavailability of curcumin.