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A common class of drug delivery nanocarriers is based on amphiphilic block copolymers (ABCs) composed of hydrophobic and hydrophilic blocks. When these polymers are dissolved in an aqueous solution at a concentration above their critical micelle concentration (CMC), they self-assemble into aggregates with a hydrophobic core and hydrophilic corona. Hydrophobic drugs can then be loaded into the core of such micelles and transported to their target in the body. This loading process however significantly affects the physical properties of a micelle, including its stability, shape, size and size distribution, and hence nanocarrier interaction with the body. In this presentation we report size distribution, morphology and specifics of cellular uptake of poly-N-vinyl-2-pyrrolidone thiooctadecylnanocarriers loaded with a hydrophobic DiI dye (as a hydrophobic drug model) prepared by ultrasonic dispersion and co-solvent evaporation methods. We observe that co-solvent evaporation technique tends to yield nanocarriers with a narrower size distribution, more regular morphology and smaller average size. However, nanocarriers prepared by ultrasonic dispersion exhibit a higher drug load and higher affinity to cellular membranes in in-vitro studies. We attribute these differences to lower thermodynamic stability of ultrasonically produced nanocarriers and discuss the experimental evidence and further implication of this phenomenon.