Many nanoparticles are designed for use as potential nanomedicines for parenteral administration. However, emerging evidence suggests that hemocompatibility is important, but is highly particle- and test-bed dependent. Thus, knowledge of bulk material properties does not predict the hemocompatibility of uncharacterized nanoparticles, including silk nanoparticles. This study compares the hemocompatibility of silk versus silica nanoparticles, using whole human blood under quasi-static and flow conditions. Substantial hemocompatibility differences are noted for some nanoparticles in quasi-static versus dynamic studies; i.e., the inflammatory response to silk nanoparticles is significantly lower under flow versus quasi-static conditions. Silk nanoparticles also have very low coagulant properties - an observation that scales from the macro- to the nano-level. These nanoparticle hemocompatibility studies are complemented by preliminary live cell measurements to evaluate the endocytosis and trafficking of nanoparticles in human blood cells. Overall, this study demonstrates that nanoparticle hemocompatibility is affected by several factors, including the test bed design.
Adsorption and desorption of fibronectin (FN) were investigated at thin films of alternating maleic acid copolymers with octadecene (POMA) and with propene (PPMA). The hydrophobicity and charge density of the polymers were modulated by the choice of the comonomer. In consequence, the dominant forces between the substrate and the protein were specified as hydrophobic interaction for POMA and electrostatic interaction for PPMA. The adsorption kinetics were investigated in situ as variations of the optical thickness, adsorbed mass, and viscoelastic properties (detected by reflectometric interference spectroscopy and quartz crystal microbalance technique, respectively) while alterations of the electrosurface properties were derived from surface conductivity data and isoelectric points (by streaming potential/current measurements using a microslit electrokinetic setup). The results demonstrate that the interfacial mode of adsorbed FN depends on the predominant interactions: large amounts of FN were tightly bound to POMA by hydrophobic interactions. In contrast, FN adsorbed on PPMA was concluded to attain an unfolded structure allowing for the "electrostatic matching" of positively charged residues on FN with the maleic acid groups. This conclusion was supported by the acidic IEP of 3.2 found for FN on PPMA and a significant reduction of the surface conductivity of the FN-covered polymer film, whereas FN on POMA showed an IEP of 4.2 (close to the intrinsic IEP of FN), indicating a stochastic orientation of the adsorbed protein.
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