From absorbable sutures to gel-like cold-and-flu capsules, polymers have been used for years in the human body to help heal what ails us.
Today, scientists are pioneering the development of new “polymer drugs”--long-chained molecules that have therapeutic benefits because of their chemical composition and high molecular weight. The potential benefits of these novel drugs range from the more precise targeting of cancer-fighting chemotherapy treatments, to the sequestering and removal of toxins in the body.
Kristi Kiick, associate professor of materials science and engineering at the University of Delaware, recently published an article on polymer therapeutics in the prestigious journal Science. UDaily talked with Kiick about this emerging field and her research team's efforts.
Q: What kinds of polymers are being used to deliver therapeutic drugs, and how do they work?
A: Many polymers have been used for controlled drug delivery without having any therapeutic benefit themselves outside of the delivery. Some polymers, though, are therapeutically active based on their structures. These polymers can be functionalized with drugs or binding agents known as ligands and potentially be targeted to the desired site in the body. For example, polymer chemotherapeutic agents have shown useful activities in treating cancer. In addition, a polymer drug called Renagel can sequester potentially harmful phosphate ions in patients with chronic kidney failure. Another polymer drug shows promise in slowing the progression of multiple sclerosis.
Q: What other advantages do polymer drugs offer in treating disease?
A: Besides opportunities for targeting, polymer scaffolds can offer certain advantages in drug efficacy such as improved solubility, increased drug loading, and increased circulation time.
Q: How do you go about designing a polymer drug, and what are some of the biggest hurdles to be leaped?
A: Some of the newest areas in polymeric drug design include making polymers that have a specific therapeutic potential based on specific details of their structure. For example, continued advances in polymer synthetic methodologies have made it possible to control the number of biologically active molecules attached to a polymer and to exert better control of the arrangement of those molecules on the polymer chain. If the biological molecule attached to the polymer can bind to cell-surface receptors, these polymers can open up many possibilities to address specific cells, since many cell-surface receptors organize into arrays, and the organization of those arrays can direct the cell into specific activities. So if one can make very well-defined polymers with the right structure, it should be possible to target specific cell types, and to control cellular activities based on controlling receptor organization.
Major hurdles include understanding the details of what the surface of the cell looks like, understanding how the polymers would interact specifically with the cell surface, and predicting what the likely cellular outcome is. There have been many advances in structural biology, polymer synthesis, molecular characterization, chemical biology and systems biology that will facilitate these types of studies and the development of new polymer drugs.
Q: What polymer drug applications are you and your laboratory group working on?
A: When I first started at UD six years ago, our primary goal was to design polymers that could bind to proteins with multiple receptors. We've been able to show that with variations in polymer structure, we can manipulate the binding event. Now we are applying that knowledge, and our abilities to produce new complicated polymers, toward polymers that can bind directly to cells and control activities such as the inflammatory response and the immune response. Polymers that could selectively engage these processes could find potential applications in biomaterials and immune therapies.
Q: How long do you think it will be until some of these novel applications are realized?
A: As the fields I mentioned previously come into more maturity, I think we will be able to purposefully design polymers with specific cellular targets in mind, and that those polymers will be able to affect cell signaling. I expect the future to be quite bright although it will be challenging to design polymers that cause a desired response in cells or in an organism without having negative effects like an immunogenic response or inflammation. It took about 25 years from the first conceptualization of a polymer drug to their routine clinical use, so it may be quite a long time before these new approaches find their way to the clinic.
Q: Why did you get into this research?
A: After working in industry, I became interested in the industrial applications of polymers and their uses as materials that we encounter every day. But my favorite classes while in school were related to biology and biochemistry. So using biological methods to produce very well-defined polymers based on amino acids, similar in some ways to structural proteins like collagen and elastin, has been almost a perfect fit to my interests and experiences. I think there are many untapped ways in which biologically derived polymers will have new uses over more traditional synthetic polymers, and I'm excited about the possibilities for applying these polymers to human health.
Q: What do you hope to achieve next?
A: Wow, that is a tough question. In the near term, we are interested in seeing if our approaches to polymer synthesis will be useful in making polymers that can target different receptor arrangements and cell types. There are a myriad of architectural features that we can manipulate, so I expect that this will keep us busy for some time. Integrating the application of these materials to complex problems such as renewable energy and sustainability may also be possible. Collaboration is a natural and necessary way to tackle these complicated problems. We are fortunate to have relevant on-campus expertise available in these interesting research areas, so a range of new research directions will be possible.
- University of Delaware