2.3.4. Surface Polymer Conformation The polymer chain conformation on the particle surface plays a critical role in conferring improved stealth properties to nanocarriers. It was found that the optimal surface coverage to confer adequate stealth properties is the one that allows for a polymer chain conformation in between the “mushroom” and “brush” configurations. In this specific

condition most of the chains are in a slightly constricted configuration, at a density to ensure no uncoated gaps on the particle surface. It is conceivable that predominant brush-like PEG configurations would sterically suppress the deposition of large proteins such as C3 convertase [25]. However, even when Inhibitors,research,lifescience,medical PEG is in the brush-like

conformation on the surface of nanoparticles, its capacity to prohibit the protein adsorption on the surface is again affected by Inhibitors,research,lifescience,medical the obstruction capacity of the protecting layer. Small molecules can, in fact, slide in between the SRT1720 molecular weight polymeric chains. For such a reason, Papisov et al. [105] highlighted the influence of (i) brush density, (ii) brush rigidity, (iii) brush molecular length, (iv) substrate size, and (v) cooperative character of interaction on steric repulsion and obstruction. The polymer chains conformation is dictated by the distance of the anchorage site of two polymer chains (D) and by the gyration radius of the polymer Inhibitors,research,lifescience,medical known Inhibitors,research,lifescience,medical as Flory radius (Rg = αn3/5, where n is the number of monomers per polymer chain and α is the length of one monomer in angstroms which corresponds

to 3.5 Å for PEG) [106]. The Rg of 2kDa PEG is approximately 5.6nm, which can be compressed depending on the surface grafting density. At low surface density, the PEG chains Inhibitors,research,lifescience,medical have higher mobility. In the case of Rg < D < 2Rg the polymer chain conformation corresponds to an intermingled “mushroom” configuration. This conformation allows the polymer chain for closer interactions to the surface of the particle and formation of gaps in the PEG protective layer that yields nanoparticle opsonisation [107]. High PEG density results in D ~ Rg and limited polymer chain motion that yields the transition from mushroom-like to mushroom/brush conformation. When D Rg, the polymer chains convert almost to a brush-like conformation. The resulting low PEG chain mobility and flexibility reduces the ability of the polymer to repulse opsonins [23]. The polymer chain movement, due to its high flexibility and mobility, reduces both of the accessible surface of the nanoparticles and the interaction of the polymer with the cryptic pockets of the opsonins [108]. Studies performed with 100nm liposomes coated with 2kDa PEG-DSPE showed that below 4% PEG-DSPE molar ratio, the PEG chains were arranged in a mushroom conformation while a brush conformation was obtained above 8% PEG-DSPE molar ratio [109]. 2.3.5.