Nanoparticles obtained with multiblock (PLA-PEG-PLA)n copolymers were found to adsorb higher amounts of proteins compared to nanoparticles obtained with polyethylene-glycol-grafted poly-(D,L) lactide (PEG-g-PLA) [115]. The low protein adsorption on PEG-g-PLA nanoparticles was ascribed to a higher surface

PEG density. Similarly, nanoparticles obtained with copolymers with a PCL Inhibitors,research,lifescience,medical backbone and PEO grafts (PCL-g-PEO) were more effective in preventing protein adsorption as compared to PEO-b-PCL diblock copolymer nanoparticles [116]. The PEG attached through both terminal groups to the nanoparticle surface formed a single-turned-coil arrangement, which was found to provide compact conformational Inhibitors,research,lifescience,medical structures that endowed particles with high resistance against blood protein adsorption [117]. The effect of linear and branched PEGs on stealth properties of nanocarriers was also investigated by using liposomes decorated with PEG-PE and PEG2-PE. PEG2-PE was more efficient in improving the blood circulation time than PEG-PE at a low content (3% mol), whereas at high molar ratio (7% mol) their effect on liposome blood clearance is almost identical. At higher ratio of protecting polymer (7% Inhibitors,research,lifescience,medical mol), even PEG-PE can provide complete coating of the liposome surface that does not take place at low molar PEG-PE ratio [108].

2.4. Controversial Effect of Polymer Coating Many studies have demonstrated that the particle opsonisation can be reduced by surface coating

with hydrophilic flexible polymers and mathematical elaborations have been developed to describe this effect. However, it should be noted that several controversial results have been reported in the literature. Inhibitors,research,lifescience,medical In vitro studies showed that stealth vesicles obtained by PEG coating can associate with a pool of opsonic proteins of serum and plasma such as click here components of the complement system and immunoglobulins. Nevertheless, it was not Inhibitors,research,lifescience,medical clear if the protein interaction occurred with the exposed or internal part of the coating polymer [14, 29, 33, 60, 118–124]. In vivo, 2.5–10% of the dose of PEG-coated vesicles and nanoparticles has been found to dispose in the liver and spleen in the first hour after intravenous administration [125–130]. The limited removal Methisazone of stealth particles from the bloodstream seems to indicate that a small amount of specific opsonic proteins can target PEG-coated nanocarriers [124]. This hypothesis is supported by the evidence that low doses (20nmol/kg body weight) of PEGylated liposomes are rapidly cleared by macrophages, while the cleared dose fraction decreases as the amount of the injected PEG-coated liposomes increased [125–127]. Stealth nanocarriers were found to display long circulation profiles even after extensive opsonisation. A typical example is Doxil, the PEGylated doxorubicin loaded liposome formulation, which is efficiently opsonised by the C3b factor and activates the complement.