This seems like such a no-brainer for tPA delivery. Without the need to deliver massive doses of it, it would be much safer to use and I bet it could be used long past the 4.5 hour limit. Get your doctor and researcher excited about this. We have to push this, no one else will.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=127855&CultureCode=en
Researchers have discovered a method that allows for the controlled
release of an active agent on the basis of a magnetic nanovehicle. The
research, conducted as part of the National Research Programme "Smart
Materials" (NRP 62), opens up new possibilities for the develop-ment of
targeted treatments, which are more efficient and trigger fewer side
effects.
Certain drugs are toxic by nature. For example, anti-cancer drugs
developed to kill diseased cells also harm healthy ones. To limit the
side effects of chemotherapy, it would be a great step forward if it
were possible to release a drug only in the affected area of the body.
In the context of the National Research Programme "Smart Materials" (NRP
62) - a cooperation between the SNSF and the Commission for Technology
and Innovation (CTI) - researchers of ETH Lausanne, the Adolphe Merkle
Institute and the University Hospital of Geneva have discovered a method
that might represent an important step towards the development of an
intelligent drug of this kind. By combining their expert knowledge in
the areas of material sciences, biological nanomaterials and medicine,
they were able to prove the feasibility of using a nanovehicle to
transport drugs and release them in a controlled manner.
This nanocontainer is a liposome, which takes the shape of a vesicle.
It has a diameter of 100 to 200 nanometers and is 100 times smaller
than a human cell. The membrane of the vesicle is composed of
phospholipids and the inside of the vesicle offers room for the drug. On
the surface of the liposome, specific molecules help to target
malignant cells and to hide the nanocontainer from the immune system,
which might otherwise consider it a foreign entity and seek to destroy
it. Now the researchers only needed to discover a mechanism to open up
the membrane at will.
Nano effect
This is exactly what the researchers succeeded in
doing (*). How they did it? By integrating into the liposome membrane
superparamagnetic iron oxide nanoparticles (SPION), which only become
magnetic in the presence of an external magnetic field. Once they are in
the field, the SPION heat up. The heat makes the membrane permeable and
the drug is released. Researchers proved the feasibility of such a
nanovehicle by releasing in a controlled manner a coloured substance
contained in the liposomes. "We can really talk of nanomedicine in this
context because, by exploiting superparamagnetism, we are exploiting a
quantum effect which only exists at the level of nanoparticles,"
explains Heinrich Hofmann of the Powder Technology Laboratory of EPFL.
SPION are also an excellent contrast agent in magnetic resonance imaging
(MRI). A simple MRI shows the location of the SPION and allows for the
release of the drug once it has reached the targeted spot.
Designed for medical practice
"To maximise the chances of
discovering an effective treatment, we focused on nanocontainers, which
would be readily accepted by doctors," adds Heinrich Hofmann. This
strategy limits the range of possibilities. Liposomes, which are already
used in a number of drugs on the market, are composed of natural
phospholipids which can also be found in the membranes of human cells.
To open them up, researchers focused on SPION, which had already been
the subject of numerous toxicological studies. More efficient materials
were ignored because little or nothing was known about their effects on
humans. In terms of shape, another important parameter of magnetism,
they chose to use only spherical nanoparticles, which are considered
safer than fibrous shapes. The intensity and frequency of the magnetic
field needed to release the active agent are compatible with human
physiology.
The combination of these parameters presented the researchers with
another challenge: to reach a temperature sufficiently high to open up
the liposomes, they were forced to increase the size of the SPION from 6
to 15 nanometres. The membrane of the vesicles has a thickness of only
4-5 nanometres. Then the masterstroke: the research group of Alke Fink
at the Adolphe Merkle Institute was able to regroup the SPION in one
part of the membrane (*). This also made MRI detection easier. Before
starting in-vivo tests, the researchers aim to study the integration of
SPION into the liposome membrane in greater detail.
National Research Programme "Smart Materials" (NRP 62)
NRP 62 is a
cooperation programme between the Swiss National Science Foundation
(SNSF) and the Commission for Technology and Innovation (CTI). It
strives to promote scientific excellence and contribute to the
successful industrial exploitation of smart materials and their
applications. NRP 62 intends to combine the expertise and resources of
various research institutions across Switzerland. The researchers will
devise the technologies needed for the development of smart materials
and for their application in intelligent systems and structures. NRP 62
consists of 21 projects of use-inspired fundamental research. It has a
budget of CHF 11 million and ends in 2015.
http://www.snsf.ch
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