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Small package, big impact
LONDON—A posting on the Imperial College London (ICL) website in early July by Ryan O'Hare of the institution’s Communications and Public Affairs department notes that scientists there have tested a new type of nanoparticle called metal organic frameworks (MOF) that they think might be useful for treating patients with pulmonary arterial hypertension (PAH). The MOFs are described as “tiny metal cages less than 100 nanometers across that can be loaded with drug molecules.”
In their study, titled “Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy” and published online in Pulmonary Circulation, the multidisciplinary group at ICL described how it has taken “the first in a number of steps” to develop nanoparticles able to deliver drugs directly to the lungs. One of their key goals for now was to demonstrate that the basic structures of the MOFs are not harmful to cells.
There is no cure currently for PAH, in which the blood vessels of the lungs “constrict and thicken, increasing blood pressure and causing the right side of the heart to work harder and harder, until it eventually fails,” as described by ICL. Existing treatments for PAH work by opening up the compromised blood vessels; however, the effects are exhibited on blood vessels throughout the body, which means a drop in blood pressure and a number of side effects. As such, the dose at which such drugs can be given is limited.
And that is where the MOFs come into play.
“The hope is that using this approach will ultimately allow for high concentrations of drugs we already have to be delivered to only the vessels in the lung, and reduce side effects,” explained Prof. Jane Mitchell of the National Heart and Lung Institute at ICL, who led the research. “For patients with pulmonary arterial hypertension, it could mean we are able to turn it from a fatal condition to a chronic manageable one.”
The MOFs are made of iron and were created in the lab of Prof. Paul Lickiss and Dr. Rob Davies from the Department of Chemistry, and by Dr. Nura Mohamed during her Ph.D. studies at ICL. Mohamed, who was funded by the Qatar Foundation, made the structures so that existing drugs used to treat PAH could fit inside them.
The research team tested the MOFs in human lung cells and blood vessel cells that were grown from stem cells in the blood of patients with PAH, and they have reported that the structures reduced inflammation while also being non-toxic to the cells. Rats injected with MOFs over a two-week period showed few side effects, other than a slight build-up of iron in the liver.
“One of the biggest limitations in nanomedicine is toxicity,” noted Mitchell, adding that “some of best nanomedicine structures do not make it past the initial stages of development as they kill cells. We made these prototype MOFs and have shown they were not toxic to a whole range of human lung cells.”
Beyond the finding that their iron nanostructures were non-toxic, ICL notes, the team believes the MOFs may have additional therapeutic properties. There was evidence to suggest anti-inflammatory properties, with the MOFs reducing the levels of an inflammatory marker in the blood vessels called endothelin-1, which causes arteries to constrict. In addition, iron is also a contrast agent, meaning it would show up on scans of the lungs to show where the drug had reached.
One of the key next steps is to determine how best to get MOFs to target their cargo to the lungs and, if they can succeed there, move on to human trials, with a goal to have a drug candidate ready to test within the next five years.
Since we don’t often cover nanotech-related drug delivery options in DDNews, this might be a good time to share a few of our more recent articles on the topic.
In September 2016, in the article “Getting into the liver with CRISPR,” we reported on Intellia Therapeutics Inc. presenting preclinical data demonstrating in-vivo gene editing through the use of lipid nanoparticles (LNPs) to deliver CRISPR/Cas9—specifically to deliver CRISPR/Cas9 components to the liver in mice and to mediate editing of target DNA within hepatocytes.
Then in October, in “Delving into a new delivery option,” came news from Oregon State University of scientists studying new drug delivery systems for Niemann Pick Type C1 disease. There is a promising compound for treating the disease that is in clinical trials, but it requires direct brain injection and causes lung damage—furthermore, the required high doses cause significant hearing loss. The team developed a new nanotech-based delivery system they believe could deliver the drug more effectively and improve its efficacy almost five times, thus enabling much lower doses.
More recently, in June of this year, the article “A new kind of gatekeeper” told of how researchers at Rice University, along with collaborators at Emory University and the Georgia Institute of Technology, have found a way to make blood vessels “leaky” by using magnets and iron-oxide nanoparticles to increase their permeability and allow large-molecule drugs through.
Imperial College London material shared (and edited/remixed) under Creative Commons license: Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)