Biodegradable nanoparticles for intravascular drug delivery

Atherosclerosis is a disease that is characterized by accumulation of lipids, cells and minerals at damaged sites of the arterial wall. It results in the development of a plaque, hardening of the artery and eventually the formation of thrombi. This leads to a decreased blood flow at the site of the plaque. Heart attacks and strokes that result from the decreased blood flow or the release of thrombi are the main cause of mortality in the western world.
Many techniques are available to restore the blood flow at the site of the atherosclerotic lesion. Percutaneous transluminal angioplasty (PTA) is used most frequently. It involves the introduction of a balloon catheter at the site of the plaque. The balloon is inflated and deflated. The inflation and deflation procedure is repeated until the plaque is deformed to such an extent that the diameter equals the original diameter of the artery.
Although the blood flow is initially restored, restenosis takes place in 30 to 50% of the patients within three to six months after the treatment. An important step in the process that leads to restenosis is the migration and proliferation of smooth muscle cells. Therefore, medication that prevents migration and proliferation of smooth muscle cells could lead to a reduction in the incidence of restenosis. As smooth muscle cell migration and proliferation take place in the first 4 weeks after treatment, sustained drug delivery for at least 1 month is desirable.
Whereas systemic administration of drugs appeared to be inefficient and is hampered by adverse side effects, local delivery of drugs seems to be a promising approach. However, drugs locally delivered as an aqueous solution had a short residence time in the arterial wall. Therefore, drug carriers were used to extend the residence time of the drug in the arterial wall. Due to their small size, nanoparticles seem to be suited as a drug carrier, and the use of biodegradable polymers for the preparation of the nanoparticles minimizes the long-term risk of adverse tissue reactions. Furthermore, the use of particles allows modification of the surface, thus enhancing the targeting of particles in the arterial wall. It was the aim of this study to prepare, characterize and surface-modify biodegradable nanoparticles that can be used for the delivery of anti-proliferative drugs to atherosclerotic vascular walls. Furthermore, the degradation behavior of nanoparticles, the release of two anti-proliferative drugs from the nanoparticles and the delivery of nanoparticles to arterial porcine carotid arteries were studied in vitro.