Polymeric nanocarriers possess advanced physicochemical properties that improve bioavailability, enhance cellular dynamics, and control target ability in drug delivery. In particular, dendritic polyglycerol is a promising new biocompatible scaffold for drug delivery. The present study explores the chemo-enzymatic modifications on dendritic hyperbranched polyglycerol (dPG) leading to amphiphilic polymeric architectures with easily hydrolysable ester linkages. Furthermore, these architectures were studied for nile red solubilization with capacity up to 5.6 mg/L at 0.1 wt % polymer conc. This corresponds to an ~10 fold increase in solubility of nile red. The release of nile red from these polymers was observed with a half life of 8 hours at pH 5.0, while no release was found at pH 7.4. The cell viability studies of our polymeric architectures showed them to be relatively nontoxic and to have the potential for future drug delivery applications.