An original encapsulation process of DHEA was developed, based on the formation of poly(ortho ester) membrane from interfacial polycondensation in an oil-in-oil emulsion. First, the formation of poly(ortho ester) (POE) in solution under anhydrous conditions between a polyol, a lactide diol and a diketene acetal (3,9-diethylidene-2,4,8,10-tetraoxaspiro-[5.5]-undecane) was studied in order to determine the structural and thermal characteristics of the POE polymer. The optimization of the formation of a fine and stable emulsion with the required size distribution was performed in relation with the type of the internal and external phases, the type and the concentration of the surfactant and the stirring rate and duration. The diffusion of monomers and DHEA was evaluated by GC-MS analysis in order to determine the mechanisms of the membrane formation. Finally the synthesis of poly(ortho ester) DHEA-loaded microcapsules was performed under anhydrous conditions required by the particular synthesis of POE. Stable poly(ortho ester) microcapsules containing DHEA were obtained with particle sizes 1 mum.