In Vivo Cellular Uptake, Degradation, and Biocompatibility of Polyelectrolyte Microcapsules**

There has been a growing interest in the design and development of polymeric microspheres as controlled release systems for drugs and antigens. Different types of polymers have been used to design biodegradable polymeric microparticles. Poly(lactic-co-glycolic) acid (PLGA) microspheres have been extensively investigated because of their biocompatibility and biodegradability. PLGA has been approved by the FDA, and GMP grade PLGA is commercially available. However, preparation of PLGA microspheres requires the use of organic solvents and involves large shear forces, both of which can seriously affect protein stability. Protein encapsulation efficiency and loading capacity of PLGA microspheres are often low. Moreover, PLGA leads to acidification of the injection site, because degradation of PLGA produces lactic acid, which can potentially denature encapsulated proteins. New types of injectable microspheres that can avoid these problems are needed. A new type of biodegradable microcapsules was recently developed using the layer-by-layer (LbL) technique. This technique is based on the sequential adsorption of oppositely charged molecules, such as polyelectrolytes, onto a charged sacrificial template (Fig. 1). The template is then dissolved, resulting in hollow capsules with a wall thickness in the nanometer