Hemocompatibility of nanocarriers designed to transport 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 =g/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 hemoreactivity.