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Micelles for the Delivery of Nitric Oxide

In the context of cardiovascular medicine, coronary arterial clotting from the fatty build-up from cholesterol is closely related to the control, volume, and coagulation of blood due to cells in the blood vessels. Angioplasty, the technique of mechanically widening an obstructed or dysfunctional blood vessel, is sometimes hampered by poor bodily reaction to a stent. A stent is a man-made ‘tube’ inserted into the blood vessel to prevent a localized blood flow constriction. To prevent the bodily reactions, focus has been placed on local drug delivery with inhibitors of cell growth and muscle contraction.

Nitric oxide has been shown to induce relaxation in cells of the blood vessel and regulate the strength and frequency of motion of the blood vessel muscles. Nitric oxide is difficult to deliver directly to the tissues and advancements in experimentation have been hampered by the rate at which nitric oxide releases into human tissue. Any current product has decomposed much too quickly to be useful as an effective drug. A current theory is to synthesize a molecule to bind nitric oxide to a binding molecule to slow the release of nitric oxide to the amounts needed over an extended time period. For effective treatment, nitric oxide would have to be released over a few weeks. Nitric oxide decomposes in less than fifteen seconds in blood vessel tissue, far too quickly for the treatment to be effective. It is necessary to control the release of nitric oxide into the tissues at a sufficiently slow rate while stabilizing it to last for extended periods of time, as the treatment is expensive and could be harmful with multiple doses every day. This can be achieved by attaching nitric oxide to a stable binding molecule but the size of the binding molecule needs to be sufficiently small to penetrate tissues under mild pressure.

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One of the routes taken by current research (J. Am. Chem. Soc., 2009, 131, 14413–14418) is to encapsulate nitric oxide into a complex of long carbon chains known as micelles. The micelles inhibit the release of nitric oxide by an average of over 50% compared to other molecules. Also, micelles have hydrophobic and hydrophilic properties, meaning that they can interact with solutions that are based of water, like blood, or they can penetrate into tissues with mostly cytosol, the fluid of the inside of cells. The micelle inhibits the release of nitric oxide and can be transported facilely through both blood and tissues, making it an efficient delivery pathway for the release of nitric oxide to inhibit cell growth and muscle movement in blood vessels, protecting stent operation by reducing bodily reaction to the stent.

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