Biodegradable nanospheres offer novel approach for treatment of
toxin exposure and drug delivery
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ARGONNE, Ill. (Oct. 20, 2006) — A new technology to clean the
blood of victims of radiological, chemical and biological terrorist
attacks is being developed jointly by Argonne National Laboratory,
the Armed Forces
Radiobiology Research Institute and The University
of Chicago Hospitals.
In addition to cleaning biological and radiological toxins from blood,
the technology shows promise for delivering therapeutic drugs to targeted
cells and organs. The technology uses components approved by the U.S.
Food and Drug Administration and a novel approach to magnetic filtration.
"The best that doctors can do for most biohazard exposure is
supportive treatment," said Michael Kaminski of Argonne 's Chemical
Engineering Division. "This new system will be designed to directly
remove the toxic agents from the bloodstream — quickly and efficiently."
"Although the immediate focus of the research centers on likely
biological, chemical and radiological warfare toxins, the technology
could be extended to other medical conditions," said Axel J. Rosengart
of The University of Chicago Hospitals. "The system may lend itself
to drug and medication overdose emergencies, for example, or treatment
of various chronic or acute illnesses."
"The key to the technology is biodegradable nanospheres 100 to
5,000 nanometers in diameter," Kaminski said, "small enough
to pass through tiny blood vessels, yet large enough to avoid being
filtered from the bloodstream by the kidneys." One nanometer is
one billionth of a meter, about 70,000 times smaller than the diameter
of an average human hair.
The particles contain a magnetic iron compound and are coated with
a type of polyethylene glycol that prevents white blood cells from
attacking them. Attached to the particles' surfaces are proteins that
bind to specific toxic agents. Intravenously injected into the patient,
the nanospheres circulate through the bloodstream, where their surface
proteins bind to the targeted toxins.
"Once the nanospheres have done their work," Rosengart said, "they
are removed from the bloodstream by a small dual-channel shunt, similar
to exchange transfusion tubing, inserted into an arm or leg artery."
The shunt circulates the blood through an external magnetic separator,
where strong magnets immobilize the iron-based particles. Clean blood
flows out of the separator and back into the bloodstream.
Advantages over current methods
This system offers a number of advantages over existing methods to
clean human blood of radioactive and other hazardous materials. Current
medical procedures to detoxify human blood are restricted to a few
types of toxins and are mainly limited to dialysis and filtration.
In addition, currently available treatments can take several hours
to complete, require the turnover and filtration of large volumes of
blood, are rather inefficient at removing toxins and can be risky for
the patient. For these reasons, current methods are mostly restricted
to patients with kidney failure and certain types of drug overdoses.
Alternative treatments exist, such antibodies and chelators — substances
that combine with and neutralize toxins. These treatments can be used
for specific kinds of toxins, but they are inefficient and can cause
serious side effects, such as allergic reactions and organ failure.
Drug delivery
Nanosphere technology is also being developed to deliver drugs, genes
and otherwise un-deliverable therapies — such as acutely toxic small
molecules, peptides and pharmaceutics — to targeted cells and organs.
The particle surfaces can be designed to provide receptor-mediated
targeting of cells, sustained drug delivery, or magnetic targeting
of organs. The nanospheres can deliver water-based or oil-based drugs.
Potential applications include:
- Biological toxin exposures
- Radiological toxin exposure and radioprotection
- Internal hemorrhage
- Brain swelling
- Stroke therapy
- Cancer therapy
- Acute trauma leading to kidney failure
The project has developed a prototype magnetic filter, has tested many
nanospheres formulations for specific toxins and is conducting ongoing
trials in vitro and in vivo. |