This work is to develop a novel dual drug delivery system that can simultaneously load and release 18-glycyrrhetinic acid (GA, a hydrophobic drug) and bovine serum albumin (BSA, hydrophilic model drug) in a single formulation. The system consists of poly(D,L-lactic) (PDLLA) microspheres embedded in calcium alginate hydrogel beads. The GA-loaded microspheres were first prepared and then dispersed in the aqueous solution of sodium alginate and BSA. The resulting suspension was dropped into aqueous calcium chloride solution to obtain the dual drug delivery system. The morphology of the microspheres and beads, the drug content and loading efficiency, the interaction between GA and PDLLA, and the drug release behaviors were studied. Scanning electron microscope (SEM) revealed that the PDLLA microspheres were homogeneously distributed in the beads. Differential scanning calorimetry (DSC) measurement suggested certain interaction between GA and PDLLA, and the crystal structure of GA was influenced by the polymer. The dual release in vitro showed a rapid BSA release but a sustained GA release in all the systems. Furthermore, the release rate of BSA was accelerated by increasing PDLLA/alginate ratio, while the release rate of GA was decreased, and the release of both hydrophobic and hydrophilic drugs could be adjusted by changing the ratio of PDLLA/alginate. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 129: 767-772, 2013