Polyion complex vesicles (PICsomes) are characterized by their unique three-layered semipermeable nanomembrane structures, in which a unilamellar PIC layer is sandwiched by poly(ethylene glycol) layers, and have gathered much attention as nano-scaled drug vehicles. Herein, the crosslinking degree of the nanomembrane in the PICsome was controlled systematically for the first time. Permeability of the PICsome nanomembrane was evaluated through a kinetic study of the release of macromolecular cargoes from the PICsome. The degree of crosslinking in the nanomembrane successfully regulated the release behavior. Moreover, the shape and size of the macromolecular solutes were found to be critical factors determining their transport from the inner aqueous phase of the PICsome to the external environment. The results indicate that the unique three-layered structure of PICsome membranes plays a key role in modulating solute transport. These findings will provide a rational strategy for the development of nanomembrane-based controlled-release systems. (C) 2017 Elsevier Ltd. All rights reserved.