Bio Nanotechnology Develops Nanocontainers For Effective Treatment of Atherosclerosis

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Atherosclerosis is the hardening of the arteries. This occurs when the walls of the arteries have a buildup of fat, cholesterol, and other substances. These substances harden and form plaque. Arteries are blood vessels that transport blood away from the heart.

Over a period of time, plaque buildup narrows the arteries and makes them stiffer. This makes it harder for blood to flow through them. Clots may eventually form and block blood flow causing a stroke. Plaque also weakens the arterial walls that can rupture (break open) causing an aneurysm. Plaque can also break off and move to other smaller blood vessels restricting blood flow there or even block it.

Atherosclerosis is usually identified with older people. A healthy lifestyle can address the situation but once there is an onset, the condition cannot be reversed. Once the arteries start to harden, the only way to avoid it from becoming worse is to monitor cholesterol levels. A healthy diet, exercise and medicine are strongly recommended.

Researchers develop a 'time bomb' to fight cardiovascular disease

In Switzerland, more than 20,000 people (37% of all deaths) die of cardiovascular disease caused by atherosclerosis each year. Treatment options are currently available to people who suffer from the disease but no drug can target solely the diseased areas, often leading to generalized side effects. Intravenous injection of a vasodilator (a substance that dilates blood vessels), such as nitroglycerin, dilates both the diseased vessels and the rest of our arteries. Blood pressure can thus drop, which would limit the desired increased blood flow generated by vasodilatation of diseased vessels and needed for example during a heart attack.

In order to increase the effectiveness of treatments against atherosclerosis and to reduce side effects, a team of researchers from UNIGE, HUG and the University of Basel have developed nanocontainers having the ability to release their vasodilator content exclusively to diseased areas.

Video: Early Progression of atherosclerosis

Nanotechnology in medicine

Though no biomarker specific to atherosclerosis has been identified, there is 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. It is by making use of this phenomenon that the team of researchers has developed a veritable «time bomb», a nanocontainer which, under pressure from the shear stress in stenosed arteries, will release its vasodilator contents.

By rearranging the structure of certain molecules (phospholipids) in classic nanocontainers such as liposome, scientists were able to give them a lenticular 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. And that's exactly the intention of this technological advance. The vasodilator content is distributed only to the stenotic arteries, significantly increasing the efficacy of the treatment and reducing side effects. "In brief, we exploited a previously unexplored aspect of an existing technology. This research offers new perspectives in the treatment of patients with cardiovascular disease..." explains Andreas Zumbuehl from the Department of Organic Chemistry at UNIGE.

The development of arterial atherosclerosis may occur when deposits of cholesterol and plaque accumulate at a tear in the inner lining of an artery. As the deposits harden and occlude the arterial lumen, blood flow to distant tissues decreases and a clot may become lodged, completely blocking the artery.

"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..." states Till Saxer of the Cardiology and General Internal Medicine Departments at HUG.

"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..." states Bert Müller, Director of the Biomaterials Science Centre (BMC) at Basel.

When chemistry gets involved

How did scientists manage to change the shape of the nanocontainers so that they resemble a lens? By rearranging the structure of molecules, 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. Once modified, the molecules are hydrated then heated to form a liquid sphere which will relax 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. The nanocontainer was injected into the system and samples were taken 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.

Quantum Day

11 June 2012

Bio Nanotechnology Develops Nanocontainers For Effective Treatment of Atherosclerosis