EFFECT OF PEO SURFACE-DENSITY ON LONG-CIRCULATING PLA-PEO NANOPARTICLES WHICH ARE VERY-LOW COMPLEMENT ACTIVATORS

The rapid uptake of injected nanoparticles by cells of the mononuclear phagocytes system (MPS) is a major obstacle when a long blood circula tion time is needed. Whereas nanoparticles made from PLA and stabilize d by surfactants (PLA-F68) are rapidly phagocytized, the rate of phago cytosis is strongly reduced in case of nanoparticles made from a diblo ck copolymer (PLA-PEO). Because of the role of the complement system i n opsonization, this difference of phagocytosis was hypothesized to be related to this system. An important complement consumption was obtai ned in 5 min in the presence of PLA-F68 particles. In the presence of a higher surface area of PLA-PEO particles possessing a high PEO surfa ce density, the consumption remained very low. When the average PEO su rface density was decreased on such particles below a given threshold, a fast and strong complement consumption occurred again. These experi mental data support the concept of steric repulsion towards proteins, by surfaces covered with terminally attached PEO chains and emphasize the prime importance of PEO surface density in such an effect. The maj or, but probably not exclusive, role of complement as an opsonin capab le of inducing a fast phagocytosis by MPS should be taken into account concerning the in vitro evaluation of nanoparticles as candidates for a long blood circulation. (C) 1996 Elsevier Science Limited