BALTIMORE, June 24 (UPI) -- Researchers have restored fat metabolism to normal levels in rodents with artherosclerosis by devising a nanoparticle "wrapper" that allows a compound to help the body break down cholesterol in arteries. They plan to test the delivery method in larger animals next.
The man-made compound D-PDMP blocks synthesis of the molecule GSL, which alters cholesterol metabolism, however the body naturally breaks down the compound too fast for it to have any effect. The nanoparticle allowed D-PDMP to stay in the body long enough for it to be 10 times as effective as without it.
"Our experiments illustrate clearly that while content is important, packaging can make or break a drug," Subroto Chatterjee, a professor of medicine and pediatrics at the Johns Hopkins University School of Medicine, said in a press release. "In our study, the right packaging vastly improved the drug's performance and its ability not merely to prevent disease but to mitigate some of its worst manifestations."
Researchers fed mice predisposed to high cholesterol and artherosclerosis a high-fat diet for several months to allow fatty plaque to accumulate in their blood vessels. Splitting them into three groups, the mice then received either a placebo, D-PDMP encapsulated in the nanoparticle, or "free-floating" D-PDMP.
The mice treated with the placebo showed high levels of GSL and high levels of bad cholesterol and triglycerides. Mice that received D-PDMP wrapped in the nanoparticle, however, had normal GSL and cholesterol levels, as did the ones that received free-floating D-PDMP. The only difference between the second two groups was that mice treated with free-floating D-PDMP needed 10 times higher doses because of how fast the drug was excreted by their bodies.
The nanoparticle is regarded as safe for humans because it is composed of a common laxative ingredient and a naturally occurring sebacic acid. D-PDMP is considered safe for animals but has not been tested in humans. Researchers said the next step was to test the drug's effectiveness on larger mammals.
The study is published in Biomaterials.