This work describes the enzymatic degradation of combined hollow capsules via layer-by-layer (LbL) self-assembly technique. They previously showed the build-up and characterization of capsules composed of synthetic [Poly(sodium 4-styrene-sulfonate)/Poly(allylamine hydrochloride)] and biodegradable (Heparin/Chitosan) polyelectrolytes. Biocatalytic response of assembled multilayer capsules provides a more functional and oriented approach in controlled release of encapsulated molecules: in this case multilayer capsule was disassembled by heparinase. Morphological change of individual capsule was assessed with Atomic Force Microscopy and Confocal Laser Scanning Microscopy. The sustained release of encapsulated FITC-Dextran model was realized under enzymatic degradation of the capsule shells by heparinase. The release profile of FITC-Dextran indicated the successful control in a concentration-dependent manner, which shows the applicability as smart drug delivery system. (c) 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44916.