Carbon nanotubes (CNTs), gold and magnetic iron oxide nanoparticles, dendrimers, polystyrene microsperes as well as polyethylenimine and polyethylenimine-graft-poly(ethylene glycol) block copolymers, and phospholipid microbubbles are solid phase platforms of drug delivery. Since water solubility is essential to use them as an infusion component, the majority of these agents must be solubilized by covalent functionalization of their surface with different chemical groups or by adsorption of amphiphilic molecules, such as poly-ethylene glycol – phospholipids (PEG–lipids) (Moghimi SM, Andersen AJ 2010J Controlle Release).
These nanoformulations often cause adverse HSRs in medical practice, which patho-mechanisms are not fully understood, but in the majority of cases it could be connected to a strong complement activation (Moghimi SM, Andersen AJ 2010J Controlle Release; Merkel OM, Urbanics R 2011 Biomaterials; Szebeni J, Bedocs P, 2012 Advanced drug delivery reviews) by different pathways. For example non-functionalized CNTs cause complement activation due to adsorption of C1q (Salvador-Morales C, Flahaut E 2006 Molecular immunology). Covalent functionalization often decrease their complement activating potential (Salvador-Morales C, Basiuk EV 2008 Journal of nanoscience and nanotechnology). Moreover, covering the structures with PEG–lipids may results in uniform particles in immunological aspects as they usually activate the complement system even les manner by lectin pathway (Moghimi SM, Andersen AJ 2010J Controlle Release; Hamad I, Hunter AC 2006 2008; Moghimi SM, Hunter AC 2001 Pharmacological reviews; Moghimi SM, Szebeni J 2003 Progress in lipid research).
Our porcine model (Link) (Szebeni J, Bedocs P, 2012 Advanced drug delivery reviews) is especially sensitive for nanoformulation colloids because of the substantial pulmonary intravascular macrophage (PIM) (Chitko-McKown CG, Blecha F 1992 Annales de recherches veterinaires Annals of veterinary research; Winkler GC 1988 The American journal of anatomy) population in pigs, which can be activated by receptor mediated by endocytosis of opsonised particles, being born a consequence of complement fragments (C3b, C5b). Although the function and the origin of these cells are similar to liver Kupffer cells (Liu Z, Davis C 2008 Proceedings of the National Academy of Sciences of the United States of America) in humans and rodents, since both cells types are responsible for the elimination of debris sized particles, PIM cells seems to have further additional immunological role in response to intravenous agents.
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