Size and surface charge effect of layered double hydroxide particles upon blood cells

Biological behavior of layered double hydroxide (LDH) toward human blood cells was evaluated with respect to the particle size and surface charge parameters. Three kinds of LDHs with different particle sizes were prepared by different synthesis routes and surface charge of the LDH was controlled by coating with citrate, malate or serine. Powder X-ray diffraction patterns and scanning electron microscopic (SEM) analyses indicated that the three LDHs before surface coating had average diameter ~ 160 nm, ~ 340 nm and ~ 1980 nm with well-crystallized hydrotalcite-like structure. According to zeta potential measurement, the surface coating with citrate, malate, and serine gave controlled zeta potential of −15.28 mV, 5.68 mV, and 36.5 mV, respectively. It was confirmed that all the six LDH samples regardless of size and surface charge did not induce serious hemolysis toward human red blood cells (RBCs), of which the value was less than 2.5% even in a high administration concentration of 10 mg/mL. However, the LDH with the largest size showed statistically a higher hemolysis ratio than the others at the high administration dose and long exposure time. The SEM showed that the large LDH particles induced membrane disruption by direct attack, while most of the LDH particles were softly landed on the RBC surface. Comparative SEM study suggested that the membrane interaction of LDH toward RBC was different from that with adherent cells. The adherent cells showed massive attachment of LDH particles on membrane periphery with active endocytosis. It was therefore concluded that LDH particles with moderate size are highly compatible to human blood cells.