Scientists from Georgia Tech, Emory University, Rochester University, and Schering-Plough Biopharma have collaborated on creating particles made out of derivatives of the polyketal polymers (hydrophobic microparticles containing biodegradable ketal linkages in their backbone), that have the capacity to deliver drugs to specific diseased tissue in the body. Polyketals have long been thought to be useful drug nanocarriers.
“The polyketal microparticles we developed are simply a vehicle to get the drugs inside the body to the diseased area as quickly as possible,” said Niren Murthy, assistant professor in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “The major advantage to using these polyketals to deliver drugs is that they degrade into biocompatible compounds that don’t accumulate in a patient’s tissue or cause additional inflammation.”
Details about the polyketals and clinical applications were described during three presentations on August 18-20 at the 236th American Chemical Society National Meeting in Philadelphia. This research – initially started in 2003 – is funded by the National Science Foundation and the National Institutes of Health.
In a presentation on August 19, graduate student Scott Wilson detailed a new polyketal derivative aimed at enhancing the treatment of inflammatory bowel disease – an illness that causes the large and small intestines to swell.
The new polymer has the advantage of stability in both acids and bases. It degrades only in the presence of reactive oxygen species, which are present in and around inflamed tissue. Cell culture experiments have demonstrated that the microparticles degraded more rapidly in cells that overproduced superoxide, a reactive oxygen species.
“Delivering proteins inside microparticles has been limited because getting the protein into the microparticles required organic solvents that frequently destroyed the proteins,” explained Murthy. “To overcome this problem, we developed a method of simply immobilizing the protein on the surface of the microparticles.”
The researchers incorporated a nitrilotriacetic acid-lipid conjugate into the polyketal. In a one-step procedure, they mixed the microparticles with the proteins and centrifuged them. That immobilized the proteins on the surface of the polyketals. Laboratory experiments conducted under physiological conditions have shown that half of the bound proteins were released within 24 hours.
Press release: Polyketal microparticles show promise as drug delivery vehicle…
Image: Scanning electron microscope image of polyketal microparticles loaded with the therapeutic enzyme superoxide dismutase, which is used to treat acute liver failure. (Georgia Tech Image: Courtesy of Niren Murthy)
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