For drug delivery, this translates to a lower systemic therapeutic amount, decreasing cost as well as deleterious side effects from potent drugs. For imaging, this find more amounts to better contrast and sensitivity

per injection amount, which is important for imaging modalities that have relatively low detection sensitivity. For example, MRI has low detection sensitivity (i.e., 10-3 to 10-5 moles/L) compared to positron emission tomography (10-11 to 10-12 moles/L). Increasing the density of targeting moieties on the surface of paramagnetic nanovectors may increase the number that Inhibitors,research,lifescience,medical bind to the intended target, thus providing more material for contrast enhancement. However, increasing ligand density will have minimal effect if nanovector delivery to the wall is limiting.44 Alternatively, the concentration of paramagnetic material loaded onto a single nanovector can be increased, thus increasing the effect of each nanovector on the MR signal. Inhibitors,research,lifescience,medical Localization of a nanovector may also be increased by attaching the nanovector to micron-sized carriers that are highly efficient in traveling to the vessel wall. For example, Ananta et al. loaded nanoscale gadolinium-based contrast agents into porous silicon microparticles and showed an enhancement

in contrast due to their geometrical confinement.48 For drug delivery, microcarriers would bind to the endothelial wall and release their nanocarrier load Inhibitors,research,lifescience,medical at the vessel wall, where they may transmigrate through the endothelium (Figure 3). This would require the design of microcarriers to release their load over a suitable time frame, perhaps involving fast-degrading polymers as a shell to release nanocarriers fairly quickly. For CVDs such as atherosclerosis that inflict larger arteries, Inhibitors,research,lifescience,medical the effective delivery of nanoparticles without a microcarrier system may be possible via the vasa vasorum that feed the Inhibitors,research,lifescience,medical wall of these arteries.

As previously mentioned, associated inflammation and angiogenesis in these vessels may provide an avenue for targeting. However, only circumstantial evidence currently exists in the literature for nanoparticles localizing to the vasa vasorum.49 Certainly, nanoparticles may not be able to enter the vasa vasorum if they originate from the lumen of the Selleck OSI-906 coronary artery.50 Figure 3. Schematics of microcarriers binding and releasing encapsulated nanovectors from blood flow at the endothelium. Conclusion Overall, there are advantages and disadvantages to differently sized particles for treatment and imaging of cardiovascular diseases. Nanoparticles are attractive as they offer low risk of vessel occlusion and avoidance of phagocytosis by macrophages, but they seem to lack efficiency in finding and binding the vessel wall from blood flow. These tradeoffs indicate an apparent need for further modification of particles by deviating from spherical shape or using micron-sized spherical carriers loaded with nanosphere cargo.