A microfluidic jet spray drying technique was used to encapsulate hydrophilic drug in uniform microparticles, while tailoring their controlled release functionalities. The effects of different matrix compositions on the release behaviour of a model drug were conducted by spray drying an aqueous polymeric dispersion of a neutral copolymer based on ethyl acrylate and methyl methacrylate (Eudragit (R) NE) as the main encapsulating matrix. Lactose and silica nanoparticles were used as additives to modify the matrix compositions, with vitamin B-12 as the model drug. Evaporation-induced self-assembly of a model drug (vitamin B-12) and the matrix materials due to their colloidal interactions produced microparticles with specific morphologies for immediate or prolonged releases. Having lactose distributed homogeneously in the matrix resulted in significantly faster and almost complete release due to enhanced swelling of the polymeric matrix with the dissolution of lactose. In contrast, silica nanoparticles existed mainly at the surface of the particles, due to the slower diffusion of nanoparticles within the droplets upon drying, which could be responsible for the initial burst release of vitamin B-12 molecules with erosion of nanoparticles upon contact with the buffer. These outcomes demonstrated the capability to tune the particle response(s) from the knowledge of material properties, with the understanding of release mechanisms elucidated from monodisperse particles of different compositions. (C) 2012 Elsevier B.V. All rights reserved.