Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 88A, Issue 4, Pages 1022-1030Publisher
WILEY
DOI: 10.1002/jbm.a.31734
Keywords
poly(N-isopropylacrylamide); nanospheres; microspheres; hydrogel; phagocytes; vascular cells; restenosis
Funding
- NIH [RO1 GM074021]
- Advanced Research Program from Higher Education Coordinating Board
- AHA Established Investigator Award
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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 drug-bearing 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 mu m) made of poly(N-isopropylacrylamide) 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 intracellular-released fluorescence and confocal fluorescence microscopy revealed that nanospheres here 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. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 88A: 1022-1030, 2009
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