Corn protein, zein being researched for drug delivery

The key to a better drug delivery method for cancer patients may be growing all across the Midwest, South Dakota State University research suggests.

Assistant Professor Omathanu Perumal and his team in SDSU's Department of Pharmaceutical Sciences have been working with submicroscopic particles to deliver medications using the corn protein, zein. Zein is a protein found in distillers grains, a co-product of ethanol production. It is different from other proteins in its unique ability to prevent water absorption. This quality of zein has found applications ranging from food packaging to chewing gums.

Researchers at SDSU are preparing zein nanoparticles for drug delivery. Nanoparticles are tiny particles that can only be seen with an electron microscope. Scientists are entrapping a medication inside the nanoparticles, which Perumal describes as approximately 500 times smaller than the diameter of a strand of human hair. The tiny size of these particles could lend assistance to new cancer therapies, where one challenge is treating the cancer cells without affecting the normal cells around it.

"We can utilize size. In general, the cancerous tissue is physiologically different from the normal tissue," explains Perumal. "One of the things we see in the tumor tissue is that the blood vessels are much 'leakier,' whereas normal blood vessels don't allow particles to be transported through them. "Therefore, if you have really small particles, they will not go into normal tissue, but they can go into the cancerous tissue. This is called passive targeting."

The drug-loaded zein nanoparticles are being delivered by injection in animal experiments, but future tests may explore oral, topical and other delivery methods. When outside objects, including medications, get inside the body, the body's immune system tries to flush them out of the body. In turn, the process affects the length of time that drugs can work in the body before being expelled. These nanoparticles, however, are so tiny that the body doesn't recognize and excrete them.

The technique SDSU researchers are exploring encapsulates drugs within the nanoparticles and delivers them to the affected site. Perumal became interested in using corn zein to form nanoparticles because it satisfied a safe, biodegradable alternative to using a synthetic ingredient and could target specific areas because of its size. The dosage frequency is also reduced because the medication stays longer in the body. Perumal adds that many people, because of religious reasons, don't take in animal proteins, which is one more reason to develop treatment options that use plant-based zein.

The team is currently working with a drug commonly used to treat breast cancer. Experiments examine how much doseage is delivered and its effectiveness compared to traditional methods of delivery. Perumal said results show the treatment meets their expectations.

Perumal's work has been funded by the South Dakota Corn Utilization Council. SDSU has filed a provisional patent and researchers are moving forward with early, pre-clinical studies using mice.

Although his team is now working with human breast cancer cells, Perumal anticipates the expansion of nanoparticle treatment for other conditions. For those with artery blockage around the heart, synthetic stents are inserted to help keep the artery open. Because the stent is a foreign object, the body sometimes tries to combat its existence, causing inflammation. By coating the stent with drug-loaded nanoparticles, Perumal hopes that this could be prevented. As the research enters its third year, Perumal will continue trials with support from the South Dakota Board of Regents.

Assistant professor Omathanu Perumal of SDSU's Department of Pharmaceutical Sciences, shown in the foreground of his laboratory, is researching delivery of cancer medications using a protein from distillers grain. Shown in the background are graduate students Preety Sahdev, right, and Vamsi Venuganti.