Many medical conditions, such as chronic pain, cancer and diabetes, require
medications that cannot be taken orally, but must be dosed intermittently, on
an as-needed basis, over a long period of time. A few delivery techniques have
been developed, using an implanted heat source, an implanted electronic chip
or other stimuli as an "on-off" switch to release the drugs into the
body. But thus far, none of these methods can reliably do all that's needed:
repeatedly turn dosing on and off, deliver consistent doses and adjust doses
according to the patient's need.
Researchers led by Daniel Kohane, MD, PhD of Children's
Hospital Boston, funded by the National Institutes of Health, have devised
a solution that combines magnetism with nanotechnology.
The team created a small implantable device, less than ½" in diameter,
that encapsulates the drug in a specially engineered membrane, embedded with
nanoparticles (approximately 1/100,000 the width of a human hair) composed of
magnetite, a mineral with natural magnetic properties. When a magnetic field
is switched on outside the body, near the device, the nanoparticles heat up,
causing the gels in the membrane to warm and temporarily collapse. This opens
up pores that allow the drug to pass through and into the body. When the magnetic
force is turned off, the membranes cool and the gels re-expand, closing the
pores back up and halting drug delivery. No implanted electronics are required.
The device, which Kohane's team is continuing to develop for clinical use,
is described in the journal Nano Letters (published online September 8, DOI:
10.1021/nl9018935).
"A device of this kind would allow patients or their physicians to determine
exactly when drugs are delivered, and in what quantities," says Kohane,
who directs the Laboratory for Biomaterials and Drug Delivery in the Department
of Anesthesiology at Children's.
In animal experiments, the membranes remained functional over multiple cycles.
The size of the dose was controllable by the duration of the "on"
pulse, and the rate of release remained steady, even 45 days after implantation.
Testing indicated that drug delivery could be turned on with only a 1 to 2
minute time lag before drug release, and turned off with a 5 to 10 minute time
lag. The membranes remained mechanically stable under tensile and compression
testing, indicating their durability, showed no toxicity to cells, and were
not rejected by the animals' immune systems. They are activated by temperatures
higher than normal body temperatures, so would not be affected by the heat of
a patient's fever or inflammation.
"This novel approach to drug delivery using engineered 'smart' nanoparticles
appears to overcome a number of limitations facing current methods of delivering
medicines," says Alison Cole, Ph.D., who oversees anesthesia grants at
the National Institutes of Health's National Institute of General Medical Sciences
(NIGMS). "While some distance away from use in humans, this technology
has the potential to provide precise, repeated, long-term, on-demand delivery
of drugs for a number of medical applications, including the management of pain."
The study was funded by the NIGMS. The article can be accessed at http://pubs.acs.org/doi/abs/10.1021/nl9018935?prevSearch=%255Bauthor%253A%2BKohane%255D&searchHistoryKey.
Founded in 1869 as a 20-bed hospital for children, Children's Hospital Boston
today is one of the nation's leading pediatric medical centers, the primary
pediatric teaching hospital of Harvard Medical School, and the largest provider
of health care to Massachusetts children. In addition to 396 pediatric and adolescent
inpatient beds and more than 225 outpatient programs, Children's houses the
world's largest research enterprise based at a pediatric medical center, where
its discoveries benefit both children and adults. More than 1,100 scientists,
including nine members of the National Academy of Sciences, 13 members of the
Institute of Medicine and 15 members of the Howard Hughes Medical Institute
comprise Children's research community.
Posted September 18th, 2009
