An implanted chip delivered daily doses of teriparatide, which is usually injected, holding out the promise of implants that can help solve adherence problems.
A microchip implanted in a patient’s body has successfully delivered regular doses of medication over an extended period, researchers reported in the February 22 issue of Science Translational Medicine
. The achievement holds out the promise of a new method of reliable dosing, especially in cases where adherence is a challenge.
In a trial that took place in Denmark starting in January 2011, microchips containing 20 doses each of the drug teriparatide, which is usually delivered via daily injection, were implanted in the bodies of 8 postmenopausal women with osteoporosis between the ages of 65 and 70 years. Subcutaneous implantation of the chips just below the patients’ waistline took 30 minutes in a doctor’s office using local anesthetic, and the chips remained in the patients’ bodies for just over 3 months. Doses were stored in pinprick-sized reservoirs (600 nanoliters each) and were released when a thin layer of platinum and titanium was melted with a small electrical current.
Teriparatide was chosen for the trial because it is potent enough for doses to fit in the chip’s extremely small reservoirs, because many patients fail to take it as prescribed due to resistance to injection, and because it must be delivered in periodic pulses. In fact, when delivered continuously, the drug results in bone loss, whereas when delivered intermittently, it results in increased bone mass and mineral density. As Michael Cima, PhD, professor of engineering at MIT and one of the study authors, explained in an interview, teriparatide must be injected daily for 18 months to 2 years, but patients lack motivation to stick with the therapy because they tend not to feel sick until they break a bone; as a result, compliance drops to 25% within 7 or 8 months.
According to the trial results, the chips delivered dosages comparable to injections with no adverse side effects. (For 1 participant, the device failed to release any drug, which was attributed to a faulty component in the circuitry involved in releasing the doses.) Efficacy of the drug was measured using markers of serum calcium, bone formation, and bone resorption, all of which were found to be quantitatively similar to those reported in earlier studies using daily injections. “This device is like an organ that we program or direct to release a chemical stimulus at certain times,” said Dr. Cima. “I see it as the new frontier for implanted electronics.”
Dr. Cima and his colleague at MIT, Robert Langer, ScD, began work on drug-delivery chips in the mid-90s and in 1999 licensed the technology to MicroCHIPS Inc, which oversaw and funded the recent trial. The primary engineering challenge, explained Dr. Cima, was designing a package that could be hermetically sealed to ensure that the drug remained stable until it was ready to be released into the body. As a polypeptide, teriparatide is less chemically stable than small-molecule drugs, so the hermetic seal was key to preserving it within the body. In addition, a layer of collagen ranging in thickness from 0.2 mm to 0.7 mm grows around the implant once it is inside the body, so the device had to be designed to ensure delivery despite this barrier. (In the trial, drug delivery did not begin until 8 weeks after implantation to allow this tissue capsule to grow.)
Cima added that participants reported little discomfort from the device, which measured 5 cm x 3 cm x 1 cm in all. “I was frankly really surprised that they could not feel this device,” he said. “They uniformly said they didn’t even think about it during the day.”
The chip is capable of 2-way wireless communication, so information on dose delivery and battery status can be sent out and the patient or doctor can change the dosing schedule—all via secure wireless link. The system can also be pre-programmed to deliver doses at specific intervals. MicroCHIPS plans to test the device with different medications over longer periods. It is currently working on chips capable of carrying up to 400 doses, allowing for a year or more of therapy. The hope is that the device could be used for a variety of different drugs that require regular injection, for diseases including cancer and multiple sclerosis. MicroCHIPS plans to file for regulatory approval for its first microchip device in 2014.
To read the study, click here
. (Registration required for access to full text.)