Some drugs cannot be delivered via a normal pill or injection because they cannot readily dissolve in water. About 40 percent of new pharmaceuticals have this hydrophobic (water-fearing) character, and like a globule of oil in water, they are unable to reach their targets in the body.
Robert Prud’homme, professor of chemical and biological engineering, addresses this problem by putting the drugs inside of nanoparticles, each about one-thousandth of the width of a human hair, which are then covered with a polymer called polyethylene glycol. The small size enables dissolution of the drug to increase their bioavailability.
Nanoparticles can also tackle a different delivery challenge presented by a growing class of drugs called biologics that, as the name implies, are made from cellular or genetic components. The problem is that they are all water-soluble, which make them easy prey for patrolling proteins that identify them as foreign and degrade them. The solution is similar: nanoparticles protect the biologics long enough for them to carry out their mission.
In addition to increasing the time that drugs spend flowing through the body, Prud’homme’s nanoparticles are capable of targeted delivery. This is necessary in the case of toxic drugs, including many cancer treatments, which would damage healthy cells if allowed to roam freely throughout the body. Prud’homme puts appendages, called ligands, on the outside of his nanoparticles that, due to their specific shape and chemical properties, attach to their target and only to their target. In collaboration with Patrick Sinko at Rutgers University, Prud’homme’s group discovered the optimum density of an appendage called a mannose ligand, used to target cells harboring tuberculosis microbes. The unexpected result was that attaching more appendages to a nanoparticle decreased its targeting effectiveness. This demonstration of the complex interplay between engineered nanoparticles and how the human body responds to them is a major theme of the Prud’homme research team. In addition to tuberculosis, the researchers are using these principles to attack cancer, inflammation, and bacterial infections.
The project receives funding from the National Institutes of Health, the National Science Foundation, Princeton’s IP Accelerator Fund and the School of Engineering and Applied Sciences Old Guard Grant.
–By Takim Williams