Controlling guest release by kinetic means generally suffers from poor reproducibility; thus, a thermodynamic means of control is suggested as an alternative. In this study, we show that core engineering of a macromolecular nanocapsule may enhance the unimolecularity and mediate guest release. A macromolecular nanocapsule is a core-shell amphiphilic macromolecule (CAM) hydrophobically derived from hyperbranched polyethylenimine (HPEI). Such a CAM is structurally unique because of its dense functional groups randomly populated in the core, which provides opportunity for core engineering. The difficulty with using a CAM is that the guest release is generally unstable and shows a two-stage character. Our results, on the other hand, indicate that, with core engineering of the CAM (in terms of its polarity and ionic nature), release of an ionic guest could be either greatly accelerated or retarded. In addition, with the appropriate guest-loading ratio, the release could become stable. It is also notable that the unimolecularity of the CAMs was greatly enhanced when ions were introduced into the core. (C) 2010 Elsevier Ltd. All rights reserved.