Jeff Bulte believes good things come in small packages -
very, very small packages. Bulte, a Johns Hopkins University faculty
member affiliated with the Institute for NanoBioTechnology,
and several of his colleagues have developed an incredibly versatile
micro-scale capsule embedded with nano-sized particles able to enhance
real-time visualization with magnetic resonance imaging (MRI) as well
as deliver a powerful therapeutic punch to diseases in animal models.
“Nanotechnology is becoming much more translational
in humans for diagnosis and treatment and for combinations of the
two,” says Bulte, a professor in the department of Radiology
at the Johns Hopkins School of Medicine and in the department of
Chemical and Biomolecular Engineering in the Whiting School of
Engineering.
Magnetic microcapsules made of a seaweed extract and ferric
oxide and filled with human insulin islets safely produced therapeutic
levels of insulin in swine for up to four weeks. Bulte, together with
Johns Hopkins colleagues Brad Barnett, Aravind Arepally and others,
recently reported these findings in Nature Medicine. By
embedding magnetic nanoparticles in a microcapsule just 350 μm
in diameter, the nano-particles are concentrated to increase the
sensitivity of MR imaging. In addition, the openings in the capsules
are large enough to release their therapeutic payload (insulin), yet
small enough to prevent the contents from coming under attack by the
body’s immune response system.
The Nature Medicine article describes one way the
microcapsules can be made and used. “What’s so
exciting is that the capsules remained stable, and they worked the very
first time,” says Bulte. “But the capsules are not
limited to diabetes; we have plans for other applications with
hepatocytes and stem cells,” he adds.
These other applications include targeted treatments for
fulminant (complete and sudden) liver failure and myocardial ischemia.
By modifying the encapsulation materials - using barium sulfate,
bismuth or a perflurocarbon emulsion instead of ferric oxide
nanoparticles, for example - researchers can apply more widely
available noninvasive imaging techniques, such as computerized
tomography, X-ray, ultrasound or fluorine imaging.
Also, filling the capsule with a different payload may provide
a different therapeutic payoff. “For imaging using
nanotechnology, the important thing is the payload—you have a
lot more bang for the buck and you increase your sensitivity with
nanoparticles,” Bulte says.
Kraitchman, another INBT affiliate, and Bulte also use X-ray
visible capsules for stem cell therapy to rapidly enhance imaging of
hindlimb ischemia in a rabbit model. The stem cell factors stimulate
arteriogenesis to help repair the strained vessels symptomatic of
ischemia, Bulte says.
In an ongoing project, capsules filled with hepatocytes are
being injected into the abdomens of swine or mice that had had their
liver function dramatically impaired by toxins. “The
hepatocytes are working as a sort of artificial organ until the toxin
is being cleared,” Bulte says. “This helps bridging
the gap during a critical time until the liver can regain function
following regeneration.”
With Arepally, an assistant professor in the medical
school’s departments of radiology and surgery, and Tom Link,
a graduate student in biomedical engineering, Bulte is working on
licensing a medical device that can exploit the properties of the
microcapsules in a more specialized way.
Animal studies also will help address some of the unknowns
about the long-term use of nanotechnology, Bulte says. “We
are running a year-long project in a swine model that will yield
important information as to how long the capsules remain stable and
continue to make insulin. We need to look at the histology of the liver
and see if there will be any undesirable host responses such as
inflammation.”
Posted 14th November 2007
