Recently, biodegradable nanoparticles based on block copolymers have attracted attention as effective drug delivery vehicles. Maximizing the amount of drug loaded into particle is the desired goal, but experimental results find loading only between 3 to about 25 wt% drug (for paclitaxel). The reasons for the low loading and variability in loading have not been fully explained. In this study, we present a model that quantitatively explains the observed phenomena. The thermodynamic model of drag loading is based on the molar free energy of the drug, which depends on the block copolymers size (entropic term), the interaction parameter between the drug and the hydrophobic core (enthalpic term), and the pressure-volume work to load the particle. The pressure-volume work, related directly to the interfacial tension between the core and the corona region, has not been previously considered with respect to drug loading. To validate the model, calculations were compared with experimental results for organic solutes, including paclitaxel, loaded into poly(ethylene glycol)-b-poly(ε-caprolactone), PEG-b-PCL block copolymer micelles. The model developed was found to predict the loading values in close agreement with experiments reported in literature.