A research to identify, understand and create new polymer additives that enhance the ability of orally administered drugs to reach the bloodstream has been undertaken by polymer chemists at Virginia Tech and pharmaceutical scientists at Purdue University. In a special edition of Carbohydrate Polymers, they introduced an all-natural polymer that can be used with a range of medicines to prevent crystallization during transport and storage; it then traverses the digestive tract until the still fully potent medicine is released from the polymer in the small intestine, where it is best absorbed into the bloodstream. Kevin Edgar, a professor of biomaterials and bioprocessing in the College of Natural Resources and Environment at Virginia Tech and an expert in polymer synthesis, approached Lynne Taylor, a professor of industrial and physical pharmacy at Purdue University, about collaboration. The team decided to combine the ability to understand how drugs, polymers, and the human body interact, with the ability to make new polymers based on natural, renewable polysaccharides, to help address the challenge of making some very important drugs more bioavailable through the creation of polymers tailor-made for this purpose.
Many important drugs are like table salt; they crystallize easily. When they do, the crystals are stubbornly difficult to dissolve. They crystallize instead of remaining dispersed, whether in the pill or after release in the digestive tract. Many medicines locked into crystals don't dissolve fast enough to work properly. If that happens, they cannot reach their target. Polymers are introduced to interfere with crystallization. "But the polymers that are presently FDA approved are not effective in meeting all the challenges," said Edgar. "They may prevent a process called nucleation but not stop growth of the crystal if it gets started. Or they may not continue to work after a period of time or if conditions are too hot or too damp. We needed to design a better polymer." The polymer would cover the dust mote and repel the sugar molecules, preventing nucleation. Stopping nucleation is relatively easy, but stopping growth is harder. The new polymers can stop nucleation and growth. Edgar and Taylor are working with natural cellulose to create derivatives known as cellulose esters. Cellulose is an abundant, renewable, completely natural polymer used by nature as the 'steel reinforcing rod' of trees and a major component of all plants. The groups have discovered that the effective design for pharmaceutical applications is cellulose omega-carboxyesters, which are cellulose esters that the researchers have enhanced with acids that already occur in the human body. For example, adipic acid, a natural acid present in sugar cane, can be attached to cellulose acetate to make an adipate ester. Cellulose acetate is already used in many medicines that people take today; it controls the rate of release of the drug. The researchers figured out how to make omega-carboxyesters that keep different kinds of medicines dispersed and prevent them from crystallizing -- in other words, creating pills with higher bioavailability. No polymers work in every drug formulation, but these are some of the most broadly effective bioavailability enhancement polymers seen. They enhance the stability and solubility of three HIV drugs, a pain reliever, two antibiotics, and five flavonoids, which are potent drug-like molecules that occur naturally in nuts, fruits, and vegetables. The final neat trick, after creating a polymer that binds the medicines so they cannot crystallize, is to make sure that polymer also knows when to let go. "The small intestine is where many medicines have the best chance to enter the bloodstream," said Taylor, "so often the ideal polymer will hang onto the drug through the acidic environment of the stomach, and then release the medicine in the benign environment of the small intestine."
Cellulose adipate esters and their cousin omega-carboxyester, cellulose acetate suberate, are no more complicated to make than those in adhesive tape and other inexpensive products, except that they are made with a different set of natural acids. Most of the cellulose omega-carboxyester just passes through the body unchanged and unabsorbed. If any of it breaks down in the gastrointestinal tract, it breaks down into things that are part of our diet anyway. Improved bioavailability means a scarce and expensive drug can be used to treat more patients and with fewer side effects. Fewer doses will be required, overall making it easier for patients to take their drugs on time every day.