special delivery
Pharmaceutical
companies aim to target
their drugs with nano precision.
By Cindy H. Dubin
Meat
cleaver or scalpel? That is one quick way to tell the difference between
a butcher and a surgeon. But that choice is also a metaphor for one hundred
years in surgical history. As technique has improved, the tools needed
have grown radically smaller.
Medicine as a whole has embraced this push toward miniaturization. To
replace machines that once could fill a cabinet, scientists have developed
portable and wearable devices and implants that deliver drugs, and diagnose
and monitor disease. Implants such as pacemakers and devices such as miniature
insulin pumps have transformed countless lives.
Now the miniaturization trend is reaching the pharmaceutical industry.
Thanks to advances in nanotechnology, drugs may soon be presented in the
form of a nanoparticulate—a nanometer-scale structure that could
enhance drug solubility and availability, as well as improve the timing
or location of its release inside the body. Thanks to nanotechnology,
pills will have less in common with the tinctures and extracts of old,
and behave as tiny medical devices in their own right.
Psivida Ltd., a biomedical technology company based in Perth, Australia,
has produced a material designed to enable drug molecules to be held in
nanoscale pockets; these pockets release tiny pulses of drug as the material
dissolves. The rate of dissolution can be tuned so that delivery can be
achieved over days or months.
 |
| An electron microscope examines a sample of BioSilicon from above. Each pore is just a few hundred nanometers wide. Its developers plan to infuse the porous structure with drugs; as the silicon framework slowly dissolves, the active ingredients would be released. |
The material, trademarked BioSilicon, is a nanostructured drug delivery
system based on elemental silicon—the same material used in the
microchip that runs a cell phone or computer. Researchers at Psivida said
BioSilicon could be used with a variety of drugs that have problematic
delivery and bioavailability characteristics.
One application for BioSilicon that Psivida is exploring is delivery of
drugs to the eyes via biodegradable implants. "The eye is a particularly
favored target due to the safety of BioSilicon," said Roger Aston,
director of strategy at Psivida. "Unlike the degradation products
from polymers like lactides and glycolides, silicic acid, the product
from BioSilicon, is a very mild acid expected to cause less irritation."
Another advantage of using silicon, Aston said, is the potential for integrating
the material with conventional silicon-based microelectronics to create
genuinely "smart" medical products."Microprocessors
are getting smaller and smaller, and we can already consider delivery
devices that release drugs through chip-based intelligence," he
said. "This will allow delivery characteristics that are essentially
processor controlled. Diagnostics in the body would be biodegradable devices
that report the health of a patient back to the doctor."
Aside from general concerns about nanotechnology, Psivida faces a hurdle
in gaining acceptance for its product: fears based on press accounts of
complications from silicone implants over the last several years. The
public is confusing silicon with silicone. Silicone is a non-biodegradable
polymer that contains other elements such as carbon. BioSilicon, on the
other hand, naturally degrades into silicic acid, a form of silicon found
in most foodstuffs, Aston said. Psivida has conducted studies in which
high doses of BioSilicon have been ingested by animals over extended periods,
and has found no evidence of toxicity.
Meanwhile, Altair Nanotechnologies Inc. of Reno, Nev., is testing microstructures
that can be used to release drugs. Ceramic microstructures—hollow,
porous spheres with large surface areas—are being considered for
drug delivery and dental compounds. Made from titanium and zirconium,
these structures can be coated inside and out with active pharmaceuticals
to provide controlled release.
ON TARGET
Biomedical engineers at the university of Texas at Austin are studying
targeted time release of medication. Pharmaceutical companies have not
been able to develop tablets or capsules that can release drugs at specific
times to specific sites within the body. The Texas researchers have developed
polymer nanospheres that can transport a drug safely through a hostile
chemical environment, such as the gastrointestinal tract, and do so in
tablets or capsules.
The nanospheres are created from hydrogels—stable, organic materials
that swell at a rate that is dependent on the acidity of their environment.
These hydrogels can be impregnated with medicines and swallowed; as they
come into contact with the acidic stomach environment, the hydrogels swell
and the drug is released. Texas biomedical engineering graduate student
Jay Blanchette said that he envisions a time when chemotherapy drugs can
be orally administered using such nano-spheres. Blanchette added that
the nanosphere composition can be tailored to deliver specific chemotherapeutic
agents.
In June, at the annual meeting of the Controlled Release Society in Honolulu,
the University of Texas team discussed the feasibility of the hydrogels
as oral delivery carriers for peptide and protein drugs that are susceptible
to damage from enzymes and acids of the stomach. (At present, these drugs
can only be administered through injection.) Test results indicated that
the hydrogels do protect this class of drugs, and that a significant fraction
of the drug would remain in the hydrogel as it passes through the highly
acidic environment of the stomach.
"The drug can bypass the stomach and the intestine and get into
the bloodstream to target therapeutic sites," said Nicholas Peppas,
professor of chemical engineering, biomedical engineering, and pharmaceutics
at The University of Texas. "This might sound like science fiction,
but it isn't anymore."
Other research groups are delving into even smaller scales to find drug
delivery systems. Quantum dots, for instance, are nanoparticles that are
smaller than the wavelength of visible light. This gives them useful optical
properties, including luminescence under ultraviolet light. They fluoresce,
or stay lit, much longer than dyes conventionally used for tagging cells.
The dot size controls the color.
According to the Institute of Nanotechnology in Glasgow, Scotland, quantum
dots can be used to develop early warning test kits for disease. Dots
are tagged to proteins and their glow enables the identification of specific
proteins or DNA, making it possible to diagnose various diseases. When
DNA in a test sample binds with a specific DNA on a quantum dot probe,
the sample fluoresces under UV radiation; this signal can then be analyzed.
Researchers can tell how much protein is on each cell by the amount of
light transmitted in a particular color. A change in the concentration
of a certain type of proteins, for example, could be an early indication
of cancer. This technique also can be designed to detect genes of harmful
pathogens ranging from Staphylococcus to anthrax.
Stephen Turner, vice president and chief technology officer at SCOLR Pharma
Inc. in Bellevue, Wash., said, "While nanotechnology is still in
its infancy, the systems and principles have significant opportunities
going forward."
In other words, while nano-enhanced drugs may have a precision far greater
than a scalpel, they may well provide the power of a sledgehammer.
|
NANO
INNOVATIONS Several
nano-based technologies are currently on their way to market or
already there. According to the Institute of Nanotechnology, these
are some emerging medical developments. |
Cindy H. Dubin is a freelance writer based in Waterford,
Mich.
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