CHAMPAIGN, Ill. -- Polyethylene glycol (PEG) is widely used for drug encapsulation and as a protective surface coating for biomedical applications. Its popularity as a surface coating has been based -- in part -- on the belief that the material forms an inert, steric barrier that prevents proteins and other biological materials from sticking to foreign or man-made materials. Recent work at the University of Illinois, however, has revealed that this polymer is not as inert as researchers thought.
Chemical engineering professor Deborah Leckband and graduate student Shailesh Sheth used a surface-force apparatus to measure the molecular forces between two membranes supporting PEG and the protein streptavidin. The researchers discovered that PEG can undergo attractive interactions with the proteins that will result in the latter binding to the polymer surface.
"Not only did the polymer switch from a protein-resistant state to a protein-attractive state, we found the presence of the protein appeared to induce a change in the polymer configuration," Leckband said. "This suggests there may be some additional structure in the polymer backbone that is important in maintaining the inert or protein-evasive property."
Leckband and Sheth's research indicates that PEG may work well for short periods -- to extend drug delivery times in the bloodstream, for example -- but over longer periods, the polymer's structure may change, making it less repulsive and potentially more biologically active.
"This is particularly important in applications such as implants and artificial scaffolds, where polymer-coated materials are in contact with living tissue for extremely long periods of time," Leckband said. "Implicit in such long-term applications is the requirement that the polymer does not perturb the various protein structures and trigger an unwanted biological response that would lead to rejection."
One of the current problems in the design of biomaterials is that there is no direct correlation between a material's properties and its biocompatibility, Leckband said. "Because of its apparent low toxicity and apparent inertness, PEG has served as a working model for the design of other surface coatings. But if your assumptions about what confers biological activity -- or the lack of biological activity -- are incorrect, you can easily head off in a wrong direction. We need to take a closer look at what fundamental material properties generate desired biological responses."
PEG's changing configuration may provide a vital clue, Leckband said. "We are now in a position to investigate at the molecular level the mechanism behind the biocompatibility properties of this material. And in learning about that we can go a step further and use that to guide the fabrication and development of new biomaterials."
Leckband and Sheth discussed their findings in the August issue of the
Proceedings of the National Academy of Sciences.