Although initially afflicted with low encapsulation efficiency of hydrophilic molecules unless w1-phase solidification was per- formed (Okada et al., 1987), the w1/o/w2 method has been described to result in extremely efficient loading of biodegrad- able microparticles with water-soluble compounds (Yamamoto et al., 1994) and is currently one of the most commonly used meth- ods for peptide and protein encapsulation. Compared to w/o-based coacervation techniques that were being developed at about the same time for hydrophilic drug encapsulation into PLGA (Kent et al., 1986), the w/o/w method was described to overcome the issues of final oil removal by several washing steps and the tendency to par- ticle aggregation during the preparation procedure (Yamamoto et al., 1994). In the literature there are a few cases where hydrophobic