A BSTRACTChitosan-coated alginate microspheres prepared by emulsification/internal gelation were chosen as carriers for a model protein, hemoglobin (Hb), owing to nontoxicity of the polymers and mild conditions of the method. The infl uence of process variables related to the emulsifi cation step and microsphere recovering and formulation variables, such as alginate gelation and chitosan coating, on the size distribution and encapsulation effi ciency was studied. The effect of microsphere coating as well its drying procedure on the Hb release profi le was also evaluated. Chitosan coating was applied by either a continuous microencapsulation procedure or a 2-stage coating process. Microspheres with a mean diameter of less than 30 ÎŒm and an encapsulation effi ciency above 90% were obtained. Calcium alginate cross-linking was optimized by using an acid/CaCO 3 molar ratio of 2.5, and microsphere-recovery with acetate buffer led to higher encapsulation effi ciency. Hb release in gastric fl uid was minimal for air-dried microspheres. Coating effect revealed a total release of 27% for 2-stage coated wet microspheres, while other formulations showed an Hb release above 50%. Lyophilized microspheres behaved similar to wet microspheres, although a higher total protein release was obtained with 2-stage coating. At pH 6.8, uncoated microspheres dissolved in less than 1 hour; however, Hb release from air-dried microspheres was incomplete. Chitosan coating decreased the release rate of Hb, but an incomplete release was obtained. The 2-stage coated microspheres showed no burst effect, whereas the 1-stage coated microspheres permitted a higher protein release.