Interaction of layer-by-layer coated hemoglobin microparticles with blood cells – An in-vitro study

Biopolymers are advantageous in the process of nano/microparticles fabrication for biological and medical applications. This is due to their great biocompatibility, stability and absence of toxicity, which forecast their potential as good drug carrier vehicles. However, for medical use, particles are most of the time directly injected in the bloodstream, and therefore must not show any impact on the immune response, avoiding possible damages that could be fatal. The co-precipitation crosslinking-dissolution (CCD) technique is a promising process of fabrication that could overcome this problem when combined with the layer-by-layer technique (LbL) allowing the fabrication of optimized nanoparticles in terms of size, a peanut-like shape and zeta potential, which are parameters of interest when used as drug carriers. This work is describing the fabrication of hemoglobin based microparticles (HbMPs) coated with different polyelectrolytes and the investigation of their hemocompatibility at different scales: phagocytosis, haemolysis, and platelets activation. Uncoated HbMPs were more phagocyted than coated HbMPs. Coated HbMPs were more stimulating erythrocytes hemolysis while compared to uncoated HbMP. Though coated HbMPs remain considered as non hemolytic according to the cut-off value of 5% defined by the international standards ISO 10993-4:2017, that address the evaluation of how medical devices interact with biological systems. The platelets activation showed ambivalent outcomes, which is the subject of a detailed discussion. Among the different particles produced, coated HbMPs did not influence phagocytosis nor the haemolysis and platelets activation process, which favour their use as potential drug carriers.