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Weighting cancer drugs to make them hit tumors harder

the amount of drug going to the tumor while reducing toxicity to the rest of the body," said Fan Yuan, Ph.D., co-author on the paper and an associate professor of biomedical engineering at Duke. "We can adjust the weight higher or lower depending upon where we want the drug to concentrate."

Even drugs with vastly elevated molecular weights � 2 million molecular weight -- achieved better concentrations in tumors than a lower molecular weight, the study showed.

Chilkoti said chemotherapy by itself is small enough to travel throughout the body via the bloodstream, causing toxicity to vital organs such as the liver, bone marrow and heart. Likewise, chemotherapy's stay inside tumors is brief because it flows out as rapidly as it entered.

In contrast, high molecular weight chemotherapy molecules are too large to be picked up by normal blood vessels. The drugs also remain longer in the tumor because they are not readily reabsorbed into the bloodstream, nor can they penetrate the kidneys to be cleared from the body. They must wait for the liver to break them up and dispose of them via the intestines.

"Our goal was to increase the tumor dose and lower the systemic dose," said Chilkoti. "Macromolecular drug carriers are an attractive drug delivery system, because they target tumors and have limited toxicity in normal tissues."

Of additional benefit, macromolecular drug carriers can be substituted for the toxic substances routinely mixed with chemotherapy to make it more soluble. Macromolecular molecules can selectively carry the drug to the tumor simply due to their size and do not need such noxious carriers, said Chilkoti.

"We can increase the solubility of chemotherapy by adding it to a soluble macromolecular molecule," he said. "Then you don't have to mix it with noxious substances as a means of ensuring that chemotherapy gets into cancer cells."

Chilkoti said their findings also are important because they can be u
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Source:Duke University


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