In a Strategy to develop more stable ultrasound contrast agents (UCAs), we have designed a process to obtain nano/microcapsules with a single core of liquid perfluorocarbon within a biodegradable polymeric shell of homogeneous thickness. During the optimization of perfluorooctyl bromide (PFOB) encapsulation by solvent emulsion-evaporation, a marked influence of surfactants has been observed. While sodium cholate leads to spherical capsules of homogeneous thickness, sodium taurocholate induces to the formation of "acorn"-particles with one hemisphere of PFOB and another one of PLGA, and polyvinyl alcohol is responsible for the coexistence of both morphologies. Whereas the theoretical model proposed by Torza and Mason [J. Colloid Interface Sci. 33 (1970) 67] fails to predict the observed morphologies, microscopic observations of the evaporation and interfacial tension measurements provide an insight into the mechanism of formation of these Structures. Most probably, there is a competition between PLGA and the surfactant stabilizing the emulsion at the dichloromethane-water interface. If PLGA is able to adsorb at the interface, the core-shell morphology is obtained, otherwise the acorn morphology is preferentially formed. When the surfactant rearrangement at the interface is long (>30 min), a coexistence of morphologies can be obtained. (C) 2008 Published by Elsevier Inc.