Nanoparticles (NPs) have been used for colon-specific drug delivery system due to their specific accumulation in the inflamed tissue in the colon and prolong presence in colon for the treatment of inflammatory bowel disease. The present study aimed to design NPs for colon-specific drug delivery via electrohydrodynamic atomization (EHDA). The NPs were prepared by dissolving prednisolone and Eudragit 5100 (EDS) in different solvents using various EDS concentrations and prednisolone/EDS weight ratios. Then, the prepared solution was sprayed using the EHDA machine. The process parameters such as applied voltage, injected distance, feed rate, and drum collector rolling rate were carefully adjusted to obtain blank and drug-loaded NPs. The EDS solution prepared from methanol offered high conductivity (93.51 mu s) with low viscosity (4.48 cP), resulting in spherical and small NPs with average diameter of 422 nm. The NPs prepared by using isopropanol and butanol as a solvent were irregular in shape. The sprayed products were changed from particle to fiber when using high concentration of EDS. High-fiber product was obtained when high applied voltage (20 kV) was applied. Size range of the NPs loaded with prednisolone at different concentrations (0.5-3.5%) was 448-660 nm. The maximum drug encapsulation was 91.50%. From the obtained results, the NPs were successfully fabricated by EHDA technique and this showed a promising potential for further drug delivery system development. (C) 2016 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.