Protein transporter in the gut could speed drug ‘take up’

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For poorly absorbed medications, drug makers should consider using natural homing devices to drive the drugs through the hazards of gastrointestinal acidity and enzymes to reach the bloodstream quicker, James Polli, PhD, said today at the annual meeting of the American Association of Pharmaceutical Scientists (AAPS) in Atlanta.

Polli, a professor at the University of Maryland School of Pharmacy, and other pharmaceutical scientists are studying ways to attach poorly absorbed drugs to nutrients to form so-called prodrugs, which then ease across cell membranes of the GI track via doors called “transporting proteins.”

Polli reported on progress using prodrugs that are based on bile acids that use a protein transporter in the gut. He said they can be used like Trojan horses to sneak drugs past barriers in the GI track because the body identifies them as nutrients, not drugs.

Polli said that the bile acid transporter technique so far works in the laboratory. “You take a drug that is poorly absorbed and link it with a bile acid, which is kind of like a homing device,” he said. Some antiviral drugs on the market already use the technique.

At this year’s AAPS annual meeting, attended by approximately 10,000 scientists, presenters in a symposium on the rapidly expanding pharmaceutical field of formulation design and drug development are sharing scientific data to answer key questions surrounding how a drug performs in the human body: Does it absorb well or mostly flush through? Does it reach the target of the illness it is designed to treat?

“For a medicine to be on the shelf, it must be safe, effective, and have pharmaceutical quality,” Polli said. “That’s a huge challenge. Then, developing new drugs that are not only safe and effective but also bioavailable, manufacturable, and portable, that’s a tough combination to come by.”

He said administering a drug intravenously if it is not absorbed well in the body, “is not acceptable in general.” Instead, the drug “can be taken up as an apparent nutrient, then yield the drug once it is absorbed into the body.”

In the human body, the normal role of the bile acid transporter in the liver or intestine is to drive proper circulation of bile acid and maintain a cholesterol balance. But recently, researchers have found that bile acids can also function as intracellular signals that alter cell behavior such as the metabolic movement of other compounds or drugs.

According to Diane Burgess, PhD, a professor at the University of Connecticut and an AAPS advisor, many drugs that are now coming into the market are very difficult to formulate because they have “delivery system problems.” Even in clinical trials, a major hurdle impeding the success of drug candidates can be poor intestinal permeability, said Polli. According to Polli, researchers are finding that targeting the intestinal lining is an attractive approach for improving bioavailability of poorly absorbed oral drugs.

The Food and Drug Administration recently awarded Polli and his research team at the University of Maryland School of Pharmacy two contracts totaling about $600,000 for new research on drug formulation for quality in manufacturing.


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