This paper introduces a novel approach to controlling membrane permeability in free unilamellar vesicles using shearing in the presence of a detergent with a large head-group to tune pore formation. Such shear-induced permeation could offer a simple means of postencapsulating bioactive molecules to prepare vesicle vectors for drug delivery. Using UV absorption, fluorescence emission, dynamic light scattering, and electron microscopy, we investigated the membrane permeability and the morphology of unilamellar lipid vesicles (diameter in the range 50-400 nm) subjected to a shear stress in the presence of a small amount of nonionic surfactant (Brij 76). Shear-induced leakage and fusion events were observed. We analyzed the significance of the vesicle size, the shear rate, and the surfactant-to-lipid ratio for the observed phenomena. The present approach is evaluated for postloading of preformed vesicles. (c) 2004 Elsevier Inc. All rights reserved.