The benefit gained by application of nanostructured drug delivery systems is highly influenced by their possible transport in the body. The affinity to cell membrane is a crucial parameter to be optimized by tuning the surface properties of nanoparticles (NPs). Poly(lactic/glycolic acid) (PLGA) NPs designed for drug delivery were stabilized with three different Pluronics (103, 105 and 108) as well as an amphiphilic monoalkyl hyperbranched polyglycerol (C18-HbPG). Their interaction with lipid bilayer was investigated in two types of arrangements using liposomes and polymeric adsorbed layer, while in the other model polymer stabilized PLGA NPs and supported lipid bilayer (SLB) were applied. Degree of adhesion of liposomes and PLGA NPs were characterized by quartz crystal microbalance (QCM) measurements in combination with the visual analysis of the surfaces by atomic force microscopy (AFM). The comparison of the various polymer coatings led to the conclusion that C18-HbPG resulted in the highest membrane affinity, followed by Pluronic105 with medium polarity within the Pluronic series. This finding further supports the results obtained previously regarding colloid stabilization efficacy (Kasza, 2017) that amphiphilic hyperbranched polyglycerol is an ideal alternative to Pluronics in the functional surface modification of drug carrier NPs.