The objective of this work was to produce drug-loaded nanometre- and micrometre-scale particles using a single-step process that provides control over particle size and size distribution. Co-axial electrohydrodynamic processing was used, at ambient temperature and pressure, with poly(lactic-co-glycolic acid) as the polymeric coating material and oestradiol as the encapsulated drug. The particle diameter was varied from less than 120 nm to a few micrometres, by simple methodical adjustments in the processing parameters (polymer concentration and applied voltage). In vitro studies were performed to determine the drug release profile from the particles during unassisted and ultrasound-stimulated degradation in simulated body fluid. An encapsulation efficiency of approximately 70% was achieved and release of the drug was sustained for a period of over 20 days. Exposing the particles to ultrasound (22.5 kHz) increased the rate of release by approximately 8 per cent. This processing method offers several advantages over conventional emulsification techniques for the preparation of drug-loaded particles. Most significantly, process efficiency and the drug's functionality are preserved, as complex multistep processing involving harsh solvents, other additives and elevated temperatures or pressures are avoided. Production rates of 1012 particles min−1 can be achieved with a single pair of co-axial needles and the process is amenable to being scaled up by using multiple sets.