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Yale bioengineers have developed a more effective method of drug delivery to
brain tumors
By adding a water-soluble polymer to an anti-cancer drug, bioengineers at
Yale and Cornell have created a modified chemotherapy that more effectively
reaches and remains at the site of brain tumors, according to a report in the
November-December issue of Bioconjugate Chemistry.
“This approach has the potential to increase treatment distances to more
than a centimeter, which may be sufficient to prevent the recurrence of human
brain tumors,” says Mark Saltzman, the Goizueta Foundation Professor of
Chemical and Biomedical Engineering and senior author on the paper.
Although placing polymer implants directly at the site of tumor is a proven
treatment for cancers of the brain, Saltzman says that success of this approach
is minimized because in most cases the drug does not penetrate into the brain
far enough for optimum treatment and there is rapid clearance of the drug from
the site.
To increase the effectiveness of their drug, Saltzman’s team attached
polyethylene glycol (PEG), an inert water-soluble polymer, to it. They also
identified a promising compound that could deliver 11 times more medication
to the tumor than the plain drug alone.
According to Saltzman, previous work on direct delivery of chemotherapy agents
to the brain has shown that drug penetration is limited by the low diffusion
into tissue. To overcome this limitation, clinical investigators have pumped
therapeutic agents at high pressure into the brain. However, this works only
as long as the pressure-driven flow is applied, and the side effects of this
continuous pumping are unknown.
“We recently conjugated — or bonded — PEG to the chemotherapy
drug camptothecin and found a substantial increase in the extent of distribution
of camptothecin in the rat brain,” says Saltzman. “This new method
using drug conjugates, which are able to diffuse through tissue and remain in
the tissue for prolonged periods, allows them to penetrate significant distances
without the need for pressure-driven flows and could substantially improve chances
for successful treatment.”
Other authors on the paper are Kraig Haverstick from Yale and Alison Fleming
from Cornell. The research was supported by grants from National Institutes
of Health.
— By Janet Rettig Emanuel
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