Homework 02

http://news.sciencemag.org/chemistry/2015/02/electric-fields-deliver-drugs-tumors

flavia@algumlugar.net (11) 99497-7773

Electric fields deliver drugs into tumors

A

Chemotherapy has been a mainstay of cancer treatment for decades. But most of these drugs aretoxic to healthy cells, and others have a hard time penetrating tumors. Now researchers report thattheyve come up with a potential solution for both problems. They used electric fields to drive chemocompounds specifically into difficult-to-treat tumors in animals, dramatically increasing the drugsconcentration within the tumor and shrinking it.

B

Like all potential cancer treatments from animal studies, the approach has a long way to go before itreaches patients. However, the strategy is encouraging, says Robert Langer, a chemical engineer at theMassachusetts Institute of Technology in Cambridge and an expert in drug delivery, who wasntinvolved with the work. The initial data look quite promising.

C

Joseph DeSimone, a chemist at the University of North Carolina, Chapel Hill, who headed up thenew study, says he became interested in working on hard-to-treat tumors after years of developingnovel approaches to deliver drugs orally. He also recently lost a close colleague to pancreatic cancer,who like other patients with the disease was ravaged by the side effects of chemo.

D

DeSimone was familiar with a different approach for delivering chemo drugs locally into tumors thatinvolves putting them in biodegradable polymers that slowly decay after being implanted next to atumor, releasing a steady supply of the drug. But that approach hasnt worked well with pancreaticcancer. Like some other tumors, pancreatic tumors build up a high internal fluid pressure, which pushesagainst medicines trying to diffuse in and prevents them from concentrating deep within the canceroustissue.

E

In the last few years, other research groups had shown that it was possible to use small electric fieldsto drive medicines into the eye and bladder. DeSimone and his colleagues wanted to see if they coulduse the same strategy to drive chemotherapeutic drugs into solid tumors. To do so, they built a setupwith a small reservoir designed to hold a liquid chemotherapy drug. This reservoir also contained oneof two electrodes that create the electric field needed to drive the drug into nearby tumor tissue. In onesetup, which was designed to deliver chemotherapy drugs to tumors deep within the body, theresearchers implanted the reservoir and its electrode on one side of a tumor, while they implanted thecounterelectrode on the tumors opposite side. In the other setup, which was designed to treat tumorsjust under the skin, the reservoir containing one electrode was placed on the skin just above the tumorin mice, while the second electrode was placed on the skin on the opposite side of the animals body.So in the latter case, the electric field generated between the two electrodes pushed the drugs throughthe skin into the tumor below.

F

DeSimone and colleagues tested their drug delivery method on mice with pancreatic or breastcancer. They also implanted their devices on the surface of the pancreas of dogs without tumors, in aneffort to better gauge the flow of drugs into tissues of larger animals such as humans. In all the studies,the devices required low electric currents and voltages, below the pain register in the animals, to drivethe drugs into the tumors. The approach works, DeSimone explains, because many liquid drugmolecules are polar, which causes them to move in an electric field toward an electrode with anopposite charge from the nearby electrode where they start.

G

The team got several promising results. In one experiment, the researchers started with mice that hadbeen implanted with human pancreatic cancer tumors. One group of mice was then implanted with theelectrode setup and administered an anticancer drug called gemcitabine twice a week for 7 weeks.Control animals received either saline through the same electrode setup or intravenous (IV) doses ofsaline or gemcitabine. The researchers report online today in Science Translational Medicine that theanimals in the experimental group had far higher gemcitabine concentrations in their tumors comparedwith mice that received the IV drug. That caused the tumors to shrink dramatically in the experimentalanimals, whereas tumors in mice that received IV gemcitabine or saline continued to grow.

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