According to Dr Mason W Freeman, Associate Professor, Harvard Medical School coronary artery disease (CAD) begins when plaques build up in the arteries. He vividly described the process. Initially, the plaque deposit may be soft and mushy; later it hardens, narrowing the artery. Blood flow to the heart decreases; at the beginning, this reduction is not severe enough to compromise heart muscle function or to produce any symptom.
Later on, the plaque may enlarge further reducing the blood flow. After a critical point, the heart muscle no longer gets adequate oxygen delivery when it is working vigorously. A prolonged or complete interruption will kill myocardial cells and cause a heart attack.
The currently available treatment options have limitations. No drug can target solely the diseased areas. Frequently drug treatment leads to generalized side effects. One method is to inject vasodilator (a substance that dilates blood vessels), such as nitroglycerin which dilates both the diseased vessels and the rest of our arteries intravenously. This can help to lower the blood pressure which would limit the desired increased blood flow generated by vasodilatation of diseased vessels and needed for example during a heart attack.
How can we make the treatment more effective? Can we reduce the side effects of treatment? One way is to deliver the drugs specifically to the diseased areas
Researchers from UNIGE, HUG and the University of Basel have developed nanocontainers having the ability to release their vasodilator content exclusively to diseased areas.
As no biomarker specific to atherosclerosis (thickening of blood vessels) has been identified, the researchers exploited a physical phenomenon inherent to stenosis (the narrowing of blood vessels) known as shear stress. This force results from fluctuations in blood flow induced by the narrowing of the artery and runs parallel to the flow of blood. Making use of this phenomenon the team of researchers developed a «time bomb», a nanocontainer which, under pressure from the shear stress in stenosed arteries, will release its vasodilator contents.
How did they design such a tiny container? By tweaking the structure of certain molecules (phospholipids) in classic nanocontainers such as liposome, scientists were able to give them a lens shape as opposed to the normal spherical shape. In the form of a lens, the nanocontainer then moves through the healthy arteries without breaking.
This new nanocontainer is perfectly stable, except when subjected to the shear stress of stenosed arteries. The vasodilator content is distributed only to the stenotic arteries, significantly increasing the efficacy of the treatment and reducing side effects.
Andreas Zumbuehl from the Department of Organic Chemistry at UNIGE. claimed that they exploited a previously unexplored aspect of an existing technology. This research offers new perspectives in the treatment of patients with cardiovascular disease,
“Nanomedicine is a discipline stemming from general nanoscience but which orients itself towards medical research. The interdisciplinary collaboration between chemistry, physics, basic science and clinical medicine in a highly technical environment could lead to a new era of research” Till Saxer of the Cardiology and General Internal Medicine Departments at HUG. noted
“The nano component is present in all disciplines, but the most interesting aspect of nanomedicine is its overview allowing the development of clinical products that integrate this global medical point of view from the earliest onset of research projects” Bert Müller, Director of the Biomaterials Science Centre (BMC) at Basel clarified.
The Chemists at UNIGE replaced the ester bond that links the two parts of the phospholipid (head and tail), with an amide bond, an organic compound that promotes interaction among phospholipids. After this modification, they hydrated the molecules and then heated them to form a liquid sphere which relaxed to solidify in the form of a lens upon cooling.
The researchers then modelled the cardiovascular system using polymer tubes blocked to varying degrees to represent healthy and stenotic arteries. Next, an artificial extracardiac pump was connected to these arteries in order to reproduce the shear stress induced by the narrowing of the vessels. They then injected the nanocontainer into the system and took samples from both healthy and stenosed areas. It turns out that the active drug was found in higher concentrations in diseased areas than in non-diseased areas and that the concentrations there were significantly greater than if the drug had been distributed in a homogenous manner.
Keep your fingers crossed, they have not yet tested the “nanobomb” on patients!