This work describes the use of a novel transepidermal drug carrier system composed of phospholipids and amphiphilc poly(amino acid)s. We polymerized poly(asparagine) grafted with octadecylamine (PAsn-g-C-18), poly(aspartic acid) grafted with octadecylamine (PAsp-g-C-18), and poly(aspartic acid) grafted with phytosphingosine (PAsp-g-PHS). We then prepared polymer hybridized liposomes (PHL) anchored with alkyl grafted poly(amino acid)s and encapsulated hydrolyzed ginseng saponins (HGS). We confirmed that the liposomes and PHL reduce the cytotoxicity of HGS, which was not observed with polymeric nanocarriers. A quantitative analysis of the amount of penetrated HGS using the Franz cell method revealed that skin permeation of the lipophilic drugs loaded in liposomes was enhanced by the incorporation of amphiphilic poly(amino acid)s. Fluorescence microscopy observations also demonstrated excellent skin permeation performance of PHL anchored with PAsp-g-PHS. PHL showed better structural stability than liposomes in an O/W emulsion. PHL considerably improved the chemical stability of HGS compared to the liposomes. It is thought that the skin permeability of encapsulated bioactive molecules could be affected by the vesicle structure, membrane fluidity, and the type of anchored polymer (C) 2013 Elsevier B.V. All rights reserved.