Herein, we report on the synthesis of PEG-1000-diethyl ester and 2-azido-propane-1,3-diol-based copolymers utilizing Novozym 435 (Candida antarctica lipase) using a biocatalytic method. The linear base copolymer was then functionalized with polyglycerol-based regular [G1.0] and [G2.0] dendrons and C-12/C-14 hydrophobic alkyl chains via an efficient Click approach. The resulting amphiphilic dendronized polymers form well-defined micelles in aqueous solutions. The transport behavior of these polymers was studied by using Nile red as a fluorescent model dye. The cytotoxicity profiles of a few representative polymers were evaluated, and the effect of hydrophobic alkyl chain length as well as the hydrophilic polyglycerol dendron's generation on the biocompatibility of polymeric systems was studied. Copyright (c) 2014 John Wiley & Sons, Ltd.