Phosphorylcholine refers to the functional group derived from phosphocholine

Phosphocholine

Phosphocholine is an intermediate in the synthesis of phosphatidylcholine in tissues. Phosphocholine is made in a reaction, catalyzed by choline kinase, that converts ATP + Choline into Phosphocholine and ADP...

. Also not to be confused with phosphatidylcholine

Phosphatidylcholine

Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically...

.

Phosphorylcholine is a zwitterionic phospholipid found on the outer surface of red blood cell

Red blood cell

Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

 membranes. It is created by CD5+/B-1 B cell

B-1 cell

B-1 cells are a sub-class of B cell lymphocytes that are involved in the humoral immune response. They are not part of the adaptive immune system,as they have no memory, but otherwise, B-1 cells perform many of the same roles as other B cells: making antibodies against antigens and acting as...

s and is referred to as a non-pathogenic autoantibody

Autoantibody

An autoantibody is an antibody manufactured by the immune system that is directed against one or more of the individual's own proteins. It is derived from the Greek "auto" which means "self", "anti" which means "against" and "body"...

.

Thrombus Resistant Stents

In the field of Interventional Cardiology

Interventional cardiology

Interventional cardiology is a branch of cardiology that deals specifically with the catheter based treatment of structural heart diseases. Andreas Gruentzig is considered the father of interventional cardiology after the development of angioplasty by interventional radiologist, Dr. Charles...

, Phosphorylcholine is used as a synthetic polymer based coating, applied to drug-eluting stents, to prevent the occurrence of coronary artery restenosis

Restenosis

Restenosis literally means the reoccurrence of stenosis, a narrowing of a blood vessel, leading to restricted blood flow. Restenosis usually pertains to an artery or other large blood vessel that has become narrowed, received treatment to clear the blockage and subsequently become renarrowed...

. The first application of this approach for use on stents evolved from efforts by Hayward and Chapman et al., who demonstrated that the Phosphorylcholine component of the outer surface of the erythrocyte bilayer was non-thrombogenic. To date, more than 120,000 Phosphorylcholine-coated stents have been implanted in patients with no apparent deleterious effect in the long term compared to bare metal stent technologies.

Phosphorylcholine Polymer based Drug-Eluting Stents

Drug-Eluting Stents are used by Interventional Cardiologists, operating on patients with Coronary Artery Disease. The Stent is inserted into the artery via a balloon angioplasty. This will dilate the diameter of the coronary artery and keep it fixed in this phase so that more blood flows through the artery without the risk of blood clots (Atherosclerosis

Atherosclerosis

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

). Phosphorylcholine is used as the polymer based coating of Drug-Eluting Stents because its molecular design improves surface biocompatibility and lowers the risk of causing inflammation or thrombosis

Thrombosis

Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...

. Polymer coatings of the stents that deliver the anti-proliferative drug, Zotarolimus

Zotarolimus

Zotarolimus is an immunosuppressant. It is a semi-synthetic derivative of rapamycin. It was designed for use in stents with phosphorylcholine as a carrier. Coronary stents reduce early complications and improve late clinical outcomes in patients needing interventional cardiology....

, to the arterial vessel wall are key components of these revolutionary medical devices. For targeted local delivery of Zotarolimus to the artery, the drug is incorporated into a methacrylate-based copolymer that includes a synthetic form of Phosphorylcholine. This use of biomimicry, or the practice of using polymers that occur naturally in biology, provides a coating, with minimal thrombus deposition and no adverse clinical effect on late healing of the arterial vessel wall. Not only is the coating non-thrombogenic, but it also exhibits other features that should be present when applying such a material to a medical device for long-term implantation. These include durability, neutrality to the chemistry of the incorporated drug and ability for sterilization

Sterilization (microbiology)

Sterilization is a term referring to any process that eliminates or kills all forms of microbial life, including transmissible agents present on a surface, contained in a fluid, in medication, or in a compound such as biological culture media...

using standard methods which do not affect drug structure or efficacy.

The ZoMaxx Zotarolimus-Eluting Stent

The third Zotarolimus-eluting coronary stent to reach clinical trials is the ZoMaxx stent. Developed by Abbott Vascular, the ZoMaxx stent was designed for thin strut width, low profile, and high radial strength, while still maintaining adequate visibility on fluoroscopy. The ZoMaxx stent delivers its antiproliferative agent through a series of Phosphorylcholine polymer coats, so that the completed stent displays experimental elution kinetics qualitatively similar to the Cypher stent. A series of in vitro and in vivo studies were conducted to establish an elution profile, which would deliver drug over a time frame consistent with events associated with the restenotic process. It was determined that drug elution could be controlled by placement of a Phosphorylcholine topcoat over a Phosphorylcholine/drug layer, and that the elution kinetics were dependent on the thickness of this top layer. Results of these studies indicated that the most rapid drug elution occurred when no topcoat was present, and that elution was slowed in a graded fashion when topcoats of increasing thickness were applied. Therefore, during the first week after implant, a Phosphorylcholine topcoat of 5 μg/mm of stent length resulted in a drug release of approximately 60% during the first week after implant, followed by an additional 20% during the second week. The remaining 20% is released over the next 2 weeks, so that virtually all the drug has been eluted over a 1-month period.

External links

• PubChem