A novel amphiphilic branched shell (ABS) obtained upon reaction of octadecen-1-yl succinic anhydride and methyl poly(ethylenglycol) (mPEG(500)) is herein presented. Through chemical attachment to the functionalized external surfaces of three different glycerol-based hyperbranched polymers (HBP), a set of novel core-ABS nanocarriers that were tested as possible candidates for dermal delivery of active substances was obtained. Pyrene has been studied as a model to evaluate the potential drug transport capability and the critical micelle concentration (CMC) of these amphiphilic systems. Subsequently, the anti-inflammatory steroid drug Dexamethasone and Finasteride, a drug widely used to prevent prostate cancer and androgenic alopecia, were also efficiently loaded into the nanocarriers. In order to promote these systems as possible candidates for dermal drug delivery, tests to evaluate the cytotoxicity on human keratinocyte cells and the penetration of the encapsulated molecules into the different layers of human skin samples were carried out. (C) 2016 Elsevier Ltd. All rights reserved.