Better Meds, Lower Cholesterol Levels are Goals of School of Pharmacy Study

$1.5 million grant from the NIH helps SOP researchers examine how bile acids travel through the gut.

By Steve Berberich
May 1, 2009

Drug makers might be able to triple the absorbing power of some medications and lower toxic risks of others, as a result of a study at the University of Maryland School of Pharmacy on how bile acids travel through the gut.

The study, by Peter Swaan, PhD, a professor of pharmaceutical sciences, and colleagues at the School of Pharmacy, has been boosted by a $1.5 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases.

Swaan says the researchers want to exploit the natural cleansing and digesting process of bile acid recycling through the gall bladder, intestines, and liver. By studying the structures of intestinal bile acid transporters, special membrane embedded proteins that ease bile acids through, perhaps drugs can be designed to better transport through intestinal membranes, which are highly complex, he says.

Swaan says that prior to the new grant, “We have made some fairly good progress. This builds on our previous work that helped us find key residues for apical bile salt [acid] transporters that play a role in drug-protein interactions. We can develop a three-dimensional model, which can be used in the rational design of novel therapeutics … for enhanced intestinal permeability.”

Many medication compounds and nutrients can get stuck in membranes in the intestine. Bile acid transporter proteins help them along. “We can determine how the compounds travel across the membrane,” Swaan adds.

Also, the study could help lower doses of drugs already on the market to make them safer and still effective and lower toxicity risks in some patients. The study could also help some drugs in manufacturers’ pipelines absorb better. About half of all drugs that are tested in clinical trials fail due to inadequate absorption into the body. The study could result in more drug candidates reaching market, says Swaan.

Swaan says he is encouraged by the results. So far they have identified a pathway in a bile acid transporter and measured its dimensions by which the bile salts go through at about 600 molecular weight (size). “This is good because most drug molecules are around this molecular size.”

Additionally, the research could provide therapies to help reduce cholesterol because bile acid transporters, by preserving a circulating pool of bile acids, are involved in maintaining a balance of cholesterol, which is a natural substance serving important functions including making cell membranes and some hormones.

“Actually this information can be transferable to [targeting] a whole host of proteins that are fundamental to life, for example, glucose, amino acids, and vitamins,” he says.

Swaan was recently named editor-in-chief of the journal Pharmaceutical Research, the official journal of the American Association of Pharmaceutical Scientists. He is director of the School of Pharmacy’s Center for Nanomedicine and Cellular Delivery.