Background/Aims: The aim of this study was to assess the effect of human hepatocyte growth factor (hHGF)-loaded poly (ethylene glycol)-b-brush poly (l-lysine) (PEG-b-P(ELGg-PLL)) copolymer on ischemia/reperfusion (I/R) injury to different organs. Methods: The isoelectric point (pI) of hHGF is 5.5, and hHGF combined with PEG-b-P(ELG-g-PLL) copolymer via electrostatic interactions at pH 7.4. The synthesized PEG-b-P(ELG-g-PLL) copolymer was analyzed using H-1 nuclear magnetic resonance (H-1 NMR) and gel permeation chromatography (GPC). The hHGF/PEG-b-P(ELG-g-PLL) complex was evaluated using a nanoparticle size instrument and transmission electron microscopy (TEM). In addition, vivo performance of hHGF/PEG-b-P(ELG-g-PLL) complex was evaluated using plasma hHGF concentration and different organs ischemia reperfusion injury in rats. Results: An in vitro investigation showed that PEGb-P(ELG-g-PLL) could serve as a potential hHGF nanocarrier with efficient encapsulation and sustained release. An additional in vivo investigation revealed that the hHGF/PEG-b-P(ELGg-PLL) complex could prolong increases in plasma hHGF concentration and protect different organs (the brain, heart and kidney) against I/R injury. Conclusion: Poly (ethylene glycol)block-brush poly (l-lysine) copolymer as an efficient nanocarrier for human hepatocyte growth factor with enhanced bioavailability and anti-ischemia reperfusion injury efficacy. (C) 2017 The Author(s) Published by S. Karger AG, Basel