AbstractThe size of particulate carriers is key to their transport and distribution in biological systems, and needs to be tailored in the higher submicron range to enable follicular uptake for dermal treatment. Oligodepsipeptides are promising nanoparticulate carrier systems as they can be designed to exhibit enhanced interaction with drug molecules. Here, a fabrication scheme for drug-loaded submicron particles from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diol (OBMD) is presented based on an emulsion solvent evaporation method with cosolvent, surfactant, and polymer concentration as variable process parameters. The particle size (300–950 nm) increased with lower surfactant concentration and higher oligomer concentration. The addition of acetone increased the particle size at low surfactant concentration. Particle size remained stable upon the encapsulation of models compounds dexamethasone (DXM) and Nile red (NR), having different physicochemical properties. DXM was released faster compared to NR due to its higher water solubility. Overall, the results indicated that both drug-loading and size control of OBMD submicron particles can be achieved. When applied on porcine ear skin samples, the NR-loaded particles have been shown to allow NR penetration into the hair follicle and the depth reached with the 300 nm particles was comparable to the one reached with the cream formulation. A potential benefit of the particles compared to a cream is their sustained release profile.