Abstract
Intensive research efforts have been placed on the development of nanospheres for targeted drug delivery for treating a variety of diseases, including coronary restenosis, cancer, and inflammatory reactions. Although most of these drugโbearing spheres are delivered via intravenous administration, little is known about the effect of sphere physical characteristics on the responses of vascular and blood cells. To find the answer, this work was aimed to investigate the cellular uptake of nanosized (100 nm) and microsized hydrogel spheres (1 ฮผm) made of poly(Nโisopropylacrylamide) by vascular cells and phagocytes under various flow conditions in vitro. We found that the cellular uptake of nanospheres depended on incubation times and sphere concentrations as well as on the introduced shear stress levels of the medium. Measurements of the intracellularโreleased fluorescence and confocal fluorescence microscopy revealed that nanospheres were internalized by endothelial cells and smooth muscle cells more than microspheres, whereas microspheres were rapidly taken up by phagocytes, especially at high concentration. Our results strongly suggest that hydrogel nanospheres are more effective as an intravascular delivery system compared to microspheres in the terms of vascular cellular uptake and biocompatibility. ยฉ 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009