Using a microchip containing 100 individual drug reservoirs, each filled with small amounts of model drug compound, a team of investigators at MicroCHIPS, Inc., in Bedford, MA, have demonstrated for the first time that it is possible, using an implanted microchip device and wireless technology, to actively control the release of drugs in the body over a prolonged period of time. The technology, described in the journal Nature Biotechnology, is unique in its use of wireless signaling, its system of reservoirs allowing precise, efficient delivery of solids, liquids or gels, and its small size.
The new device is not expected to replace all pills or other forms of drug delivery. Rather, it will deliver proteins, small molecules and other drugs that are highly potent, have limited stability, and must be delivered in precise doses at specific times.
"This research is an important step toward development of novel drug delivery systems in which small devices filled with potent, therapeutic drugs are used to release medicines into the body as needed," said John Santini, Ph.D., one of the developers of the new technology. Santini, along with Robert Langer, Ph.D., co-director of the MIT-Harvard Center of Cancer Nanotechnology Excellence, and Michael Cima, Ph.D., another member of the MIT-Harvard CCNE, began work on the concept of so-called "intelligent drug delivery devices" more than a decade ago.
The MicroCHIPS teams began the current research by developing microchips made of silicon, each the size of a postage stamp and containing 100 tiny "wells" or "reservoirs." According to James Prescott, Ph.D., a member of the team, "We filled the reservoirs with a model polypeptide drug known to be poorly absorbed when taken orally. Each reservoir was capped with an electrically-erodable membrane made of platinum and titanium. Filled chips were then sealed and connected to a titanium case containing electronic hardware, power, and wireless connectivity. We also combined custom software with "off-the-shelf" electronic components and a handheld wireless communication device for use in sending data back and forth." Finally, the scientists implanted chips beneath the skin of six dogs.
For the first month of the study the investigators used a wireless signal to simultaneously release the drug from 10 reservoirs once a week. Then, for the next two months, the researchers simultaneously released doses from five reservoirs once every two weeks. For the last three months of the study, they simultaneously released doses from four reservoirs once a month. In this way, the investigators demonstrated that they could control the release of drugs in the body via a wireless device and that it was possible to do so for at least six months.
The current study, which used a microprocessor and a power source, demonstrates the feasibility of what Santini calls "active" reservoir control. According to Santini, while one important use of reservoirs is to contain drugs for release, reservoirs can also be used to selectively expose biosensors in order to monitor and provide feedback on conditions in a patient's body. Biosensors may one day be interactively paired with drug delivery.
This work is detailed in a paper titled, “Chronic, programmed polypeptide delivery from an implanted, multireservoir microchip device.” An abstract of this paper is available through PubMed.
View abstract.
