15 April 2016. An engineering and medical research team developed an implanted device that in lab mice delivers chemotherapy directly to cancerous tumors in the pancreas. The device, designed in a biomedical engineering lab at Massachusetts Institute of Technology and Harvard University, is described in an article appearing 31 March 2016 in the journal Biomaterials (paid subscription required).
The technology, created in the lab headed by engineering and medical professor Elazar Edelman, seeks to offer people with pancreatic cancer more and better therapeutic options. Pancreatic cancer is often difficult to diagnose in its early stages, due to few unique symptoms associated with the disease, as well as the pancreas being hidden among other organs in the body. As a result, it is often diagnosed in later, more advanced stages of the disease, with generally a poor prognosis for survival. American Cancer Society estimates more than 53,000 people in the U.S. will be diagnosed with pancreatic cancer this year, leading to nearly 42,000 deaths.
Another characteristic of pancreatic cancer is a thick fibrous coating that builds up on tumors, making it more difficult for drugs to penetrate. In addition, tumors in the pancreas have fewer blood vessels, limiting the routes available to deliver drugs.
The overcome these obstacles, MIT postdoctoral researcher Laura Indolfi in the Edelman lab, with David Ting and Matteo Ligorio at Massachusetts General Hospital, affiliated with Harvard Medical School, developed a flexible plastic film, loaded with chemotherapy drugs that fits over a tumor in the pancreas. The film itself is made from poly lactic-co-glycolic acid or PLGA, a biocompatible and biodegradable polymer often used in medical devices and for drug delivery.
Because of its flexibility, the film can be rolled up and delivered with a catheter to the cancer site, which unfolds and wraps around the tumor, or surgically implanted. The film is first loaded with enough chemotherapy drugs for 60 days, and programmed to release the drugs over that period. In addition, the device emits the drugs only from the side of the film facing the tumor, to limit damage to other organs.
The researchers tested the device on lab mice grafted with human pancreatic tumors. Some of the mice received the implanted device with the chemotherapy drug paclitaxel often given to treat sold tumor cancers, while the other mice received injections of paclitaxel, similar to current chemotherapy delivery methods, for 4 weeks.
After 4 weeks, mice with the device-delivered drugs had 5 times higher concentrations of paclitaxel in their tumors than mice receiving the drug through injections. Moreover, mice with the devices were found with 12 times less tumor growth, and in some cases shrinkage of tumors, than those with injected drugs. In addition, mice receiving drugs through the device had less metastasis, or spreading, of the cancer to other organs.
The authors say this drug delivery technology may have other uses. People with pancreatic tumors sometimes encounter blockages in their bile ducts from the spread of the cancer, a painful condition that interferes with digestion. Combining the drug-coated film with a stent could relieve the blockage and prevent the cancer spreading again to the duct, extending the lifetime of the stent. The device could also treat other solid tumor cancers that are difficult to reach and those needing high doses of chemotherapy, but would be too toxic to patients if delivered with conventional infusions.
Indolfi, Ting, and Edelman founded PanTher Therapeutics in 2014, a company in Boston commercializing the drug delivery technology. Indolfi is PanTher’s CEO and co-author Ligorio is the company’s lead clinician. PanTher is planning clinical trials of its device and is seeking partners to expand the technology to other disorders.
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