Protein adsorption into polymersomes: effect of chain length on circulation time in vivo

The adsorption of immunoproteins onto drug-carrying nano-particles such as liposomes enables their recognition by reticuloendothelial cells which mediate the clearance process in vivo. The attachment of polyethylene glycol (PEG) chains to the liposomes has been shown to reduce protein adsorption and enhance circulation time in vivo. Previous analysis of the effect of PEG on protein adsorption focused on supported monolayers or bilayers, thereby ignoring one of the essential features of bilayers, namely, self-assembly. We show here that bilayer reorganization significantly affects the equilibrium concentration of proteins in bilayers, elucidating the effect of the chain length and concentration. In this study, we present a simple model of proteins embedded or adsorbed onto polymeric bilayers as a function of the polymer chain length (N). We find that the probability of protein adsorption into the bilayer peaks at a specific bilayer thickness, which, most likely, corresponds to natural bilayers´ dimensions. As a result, we predict that the concentration of proteins decreases and in vivo circulation time increases as a function of polymer molecular weight. Fitting our results to a power law yield a relationship where circulation time roughly scales as N^0.4.