We reported the stepwise formation of biocompatible poly(L-lysine)/poly(L-glutamic acid) (PLL/PGA) multilayer films on mesoporous silica (MS) spheres via layer-by-layer (LbL) self-assembly technique. In-situ QCM revealed the nonlinear (exponential) growth of PLL/PGA multilayer films at both pH 5.5 and pH 7.0 conditions. xi-Potential measurements of the multilayer coated particles indicated that the multilayer surface was being charge-overcompensated in each adsorption step, thereby facilitating adsorption of the next oppositely charged polypeptide onto the MS spheres. Hollow polypeptide capsules could be obtained by Subsequently removing silica cores in HF solution. By using enzyme-preloaded MS spheres as capsule templates, a general approach was developed for encapsulating enzymes in biocompatible microcapsules with high loading and retained bioactivity. The loading amount for several enzymes with different sizes and their bioactivity after encapsulation were also reported. (c) 2009 Elsevier Inc. All rights reserved.