Block copolymer 'stealth' nanoparticles for chemotherapy: Interactions with blood cells in vitro

Passive targeting is one of the approaches to reduce the side effects in intravenous chemotherapeutic administration. This is usually achieved by using so-called 'stealth' particles as carriers, such that the particles can avoid uptake by cells of the reticulo endothelial system (RES) and thus enhance their blood lifetime. To date, there have been no studies of the contribution of various factors to the uptake of particles by the RES, although there is general agreement that a hydrophilic particle surface is helpful. In this study, data is presented on the effect of particle size and surface chemistry on the uptake by monocyte cell lines, as well as by cells in whole blood. Block copolymers of hydrophilic poly(ethylene glycol) (PEG) and the hydrophobic poly(L-lactide) (PLA) have been used to study surface concentration and conformation effects. It is found that diblock copolymers, in general, show the best stealth characteristics, although triblocks with PEG segment lengths above a certain value are also comparable. It is also found that the uptake goes through a minimum with respect to particle size. For the first time, a method is presented to evaluate the relative uptake efficiency of various types of blood cells, using flow cytometry. The observations are related to structural features found on the polymers.