Dec. 18, 2003 ATHENS, Ohio – Scientists have developed biodegradable polymers that can mimic the ability of white blood cells to target inflamed blood vessel walls, according to a new study led by Ohio University researchers. The finding could be the first step in developing drugs that suppress specific sites of inflammation in medical conditions such as arthritis, heart disease and inflammatory bowel disease.
Researchers found that biodegradable beads coated with targeting molecules can travel through the bloodstream and effectively stick to the site of tissue inflammation, a symptom of various diseases, according to the study, which will be published in the Dec. 23 issue of the journal Proceedings of the National Academy of Sciences. Scientists are interested in drugs made from biodegradable polymers because they can be easily prepared, have a long shelf life and can be designed to release specific doses of medication, according to the study.
When the body suffers from a bacterial infection or a wound, the white blood cells, or leukocytes, adhere to the site to treat the problem. But in inflammatory diseases such as arthritis, heart disease or inflammatory bowel disease, leukocytes accumulate in an area where they aren't needed and cause or progressively worsen the disease.
To address that issue, Ohio University researcher Douglas Goetz and colleagues Justin Hanes of Johns Hopkins University, Kevin Shakesheff of the University of Nottingham in England, Mohammad Kiani of the University of Tennessee Health Science Center and David Kurjiaka of Ohio University have been studying whether biodegradable particles could be used to mimic the activity of leukocytes, traveling to the exact site of the inflammatory disease in the body and delivering treatment. Conventional drugs treat pathological inflammation, but may impact healthy tissue too.
"Can we take a particle and give it the same surface chemistry as the leukocyte and make it go where the leukocyte goes?" asked Goetz, an associate professor of chemical engineering whose research is funded by the National Science Foundation and the Whitaker Foundation.
The new study suggests that in animal models, a biodegradable bead can be coated with targeting molecules and show the same level of adhesion as leukocytes. Shakesheff originally developed the bead, which is made of polylactic acid and polyethylene glycol, two polymers commonly used in other medical applications, Goetz said. This biodegradable particle was 100 times more effective at sticking to the blood vessel wall than other materials tested in previous studies, the engineer said.
The bead degrades and converts to lactic acid, a substance normally found in the body. Goetz and colleagues, using novel polymers developed by Hanes, next will test different polymers – as well as smaller nanoparticles -- that could degrade even faster in the body and offer different drug delivery options, he said. Quick degradation also could help avoid uptake by organs not intended to receive the particles, he said, a possible negative side effect of the process.
The research team also will further examine another interesting finding from the study: The biodegradable particles not only mimic the leukocyte's ability to stick to tissue, but its tendency to roll along the blood vessel wall. Though Goetz is unsure what impact this finding will have on drug delivery at this point, "it demonstrates how well we can control these particles – not only with selective delivery, but also the type of relationship they have with the vessel wall," he said.
Goetz, who next will study the drug delivery potential for chronic inflammatory conditions, hopes that the combined cell adhesion/drug delivery approach to addressing inflammation-related illnesses will progress in the next 10 years. Other scientists are making progress in creating a targeted drug delivery process to eradicate cancerous tumors, but applying such concepts to inflammatory diseases will call for some fine-tuning, he said. "Applying this to inflammation is a whole different ball game," Goetz said. "A patient probably won't die from arthritis; it's a much more subtle problem."
Other collaborators on the study are Harshad Sakhalkar, an Ohio University graduate student in chemical engineering; Milind Dalal, a former Ohio University graduate student in chemical engineering; Aliasger Salem of the University of Nottingham; Ramin Ansari of the University of Tennessee Health Science Center; and Jie Fu of Johns Hopkins University.
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