Studies carried out using PEGylated erythrocytes showed that the complement activation may be mediated by anti-PEG IgG and IgM [139]. Anti-PEG IgM elicited by a first administration of PEGylated liposome forms immunocomplexes

with the second dose of liposomes [140]. These complexes activate the complement and convert the C3 component into C3b. The complex formed by C3b with other complement components is involved in the antibody-mediated complement activation pathway [134, 141] that yields C3b fragmentation to iC3b operated by factors H and I. iC3b is a proteolytically inactive product of the complement fragment Inhibitors,research,lifescience,medical C3b that can still opsonise. However, it cannot participate in the complement cascade Inhibitors,research,lifescience,medical since it does not associate with factor B, a component of the alternative activation pathway in the early stage of the activation. The generation

of iC3b prevents the amplification of the complement cascade. Overall the PEG molecules on the liposome surface do not interfere with production of opsonic components from Inhibitors,research,lifescience,medical the C3 component. Complement activation has been suggested to account for the clearance of PEGylated liposomes by the macrophage uptake of the RES [142]. Furthermore, the extent of the accelerated blood clearance (ABC) of PEGylated liposomes is inversely proportional to the dose probably because of the saturation of the mononuclear phagocytic system [143]. 2.4.2. Poloxamine Inhibitors,research,lifescience,medical Induced Complement Activation Similarly to PEG, Poloxamines and Poloxamers have been extensively used to endow nanocarriers with stealth properties. Nonetheless, even these materials have been

found to activate the complement to some Inhibitors,research,lifescience,medical extent thus reducing the beneficial effect on particle opsonisation. Poloxamine-908-coated polystyrene nanoparticles were found to activate the complement through a complicated pathway. The adsorbed poloxamine-908 on the polystyrene nanoparticles rearranges from flat mushroom-like to brush-like selleck chemicals conformation as the density of the polymer on the particle surface increases. As the polymer packs on particle surface, the surface area occupied by poloxamine decreases from 45 to 15nm2/poloxamine Phosphoprotein phosphatase chain. The intermediate mushroom-brush poloxamine conformation induced remarkable complement activation that decreased when the polymer rearranged to a brush-like structure. Uncoated nanoparticles and particles coated with poloxamine in the mushroom-like conformation promote surface association of the C1q fragment of the complement protein C1 and activate the complement through the classical pathway. Naked and poloxamine-coated nanoparticles in the mushroom and mushroom-brush conformation also activate the complement through the alternative pathway by covalent conjugation of properdin to poloxamine and the C3 component adsorption.