In vitro hemocompatibility of nanocarriers tailored for biopharmaceutical drugs.

The optimization of nanoparticles (NP) for drug delivery, in particular to target the BBB, imposes to verify their hemocompatibility both for toxicological and efficiency of targeting perspectives. Indeed the large surface they are able to expose to the biological environment promotes their interaction with various biochemicals, in particular proteins which can after adsorption elicit the activation of biological cascades either responsible from NP clearance or/and harmful body reaction (inflammatory / coagulation). In the frame of the European Integrated Project : “Nanobiopharmaceutics”, we have the opportunity to compare the hemoreactivity of about 145 different NP samples differing in core and surface chemistry and classified according to their expected difference in hydrophobicity based on the nature of their core materials. According to this classification, PLGA nanoparticles, polyglycidol-polyethyethylene oxide nanoparticles, polyglycidol thyolated or polyacrylamide nanogels, and polyelectrolyte complexes either based on polyamidoamine or poly(N,N-dimethylamino- 2-ethylmethacrylate) have been evaluated within a concentration ranging from 0.3 to 1000 μg/mL. These in vitro tests have been realized for screening purpose adopting normal human bloods and according to Iso 10993. As a summary of this extensive study, our results clearly highlight that most of the polymeric nanoparticles evaluated give rise to some alterations of the blood components. In particular the platelets, intrinsic pathway of coagulation and complement activation are the most reactive biological parameters in the presence of these nanostuctures. Although not strictly related to the surface chemistry our classification has also allowed us to derive some clear correlations between nanomaterial properties and their hemoreactivity. Within the class of polyelectrolyte electrolyte complexes, the modifications brought in the surface chemistry has drastically improved their hemoreactivit