A new drug-delivery system for cancer of the brain -- one of the most difficult cancers to treat -- has the potential to carry anticancer drugs 10 times deeper into tumors than conventional medications, researchers in Connecticut and New York report.
Implants with anticancer drugs inside plastic or polymer material have been used for years to treat brain tumors, which occur in people of all ages but are the leading cause of cancer-related death in patients under age 35.
Although this method delivers high doses of medication to the tumor, there's a need for a drug that penetrates deeper into the brain tissue to kill tumors. Most drugs diffuse barely a few millimeters from the implant site, the researchers say.
In the new study, Mark Saltzman and colleagues showed that linking the anticancer drug campothecin (CPT) to the polymer polyethylene glycol (PEG), increased drug diffusion to more than a centimeter from the implant site.
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," said 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."
They also identified a promising CPT-PET compound that could deliver 11 times more medication to the tumor than the plain drug alone. For patients, those advantages could substantially improve chances for successful treatment, the researchers indicate.
Journal article: "Conjugation to Increase Treatment Volume during Local Therapy: A Case Study with PEGylated Camptothecin" Nov./Dec. issue of ACS' Bioconjugate Chemistry, DOI: 10.1021/bc700214h.
Materials provided by American Chemical Society. Note: Content may be edited for style and length.
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