This work investigated the means for the efficient encapsulation of muramyl dipeptide (MDP) in poly(epsilon-caprolactone) (PCL) microparticles (MP) by a solvent evaporation method in order to optimize the effect of the adjuvant for oral immunization. Therefore, the influence of MDP concentration in the inner aqueous phase was evaluated on MP characteristics such as size, morphology, drug entrapment, entrapment efficiency and the eventual interactions of MDP with co-entrapped model antigen, bovine serum albumin (BSA). The process of manufacturing produced a high entrapment efficiency of MDP (63.58 +/- 0.40%) without altering its integrity, as shown by chromatogram peaks analysis of ct and beta anomers. The crystallinity of the polymer was dramatically increased (+24.6%) either with or without MDP loading but the entrapment of BSA reduced this crystallinity suggesting BSA-PCL interaction. These MP were resistant to simulated gastric fluid and exhibited a continuous BSA release. Moreover, their average diameter (<10 mu m) combined with their high hydrophobicity make of this delivery system an exciting alternative for enhanced oral immunization.