Where a Pill Won't Reach; April 2003; Scientific American Magazine; by Robert Langer; 8 Page(s)

From the point of view of a drug, it's a long trip from the pill bottle to an ache or the site of an infection. After someone swallows a medicine, the chemical must traverse a veritable maze. It has to survive a journey through the stomach and reach the intestines intact before crossing the intestinal wall into circulation. Once in the blood, it gets filtered through the liver before it can travel to the rest of the body. At each "way station," the compound must resist the acids of digestive juices, jump membrane barriers or fend off enzymes designed to chop it into useless bits.

Pharmaceutical makers have come up with various solutions to help certain medicines on the market today surpass these obstacles; however, these approaches do not work for many other drugs. One strategy, for instance, coats pills with a shell that is insoluble in stomach secretions but that dissolves readily once it hits the more alkaline environment of the small intestine. But if a drug is made of protein-as most agents produced using biotechnology are-it also has to evade the activity of protein-destroying enzymes called proteases. Packaging pills with their own bodyguards (in this case, molecules called protease inhibitors) could enable protein-based drugs to survive, but it would not aid them in crossing the gut lining; they are too big to slip into the blood as easily as more typical drugs, which generally consist of small molecules. Coatings also have a limited ability to control a drug's pharmacokinetics-the rate at which it enters circulation and the time it persists in the body's tissues and organs. A drug can be toxic if it gets into the bloodstream too quickly at high concentrations or if it sticks around too long; conversely, it can be ineffective if a protracted delay occurs before it begins circulating.