Pharmaceutical research has been focussed on developing improved delivery systems while exploring new ways of using approved excipients. The present work investigated the potential of starch nanocapsules (StNC) as a topical delivery platform for hydrophilic antimicrobial drugs using minocycline hydrochloride (MH) as a model drug. Thus, a quality by design approach was used to assess the role of different factors that affect the main pharmaceutical properties of StNC prepared using an emulsification-solvent evaporation method. Full characterisation was performed in terms of particle size, encapsulation efficiency, morphology and physical stability at 5 +/- 3 degrees C. Results show the surfactant and lipid contents play a major role in StNC particle size distribution. The MH loading only promoted minor changes upon StNC properties. Formulations were stable without variations on physicochemical properties. All tested formulations presented a zeta-potential of +33.6 +/- 6.7 mV, indicating a good physical stability and evidencing that StNC are suitable nanocarriers for topical use.