Design and synthesis of thermo-responsive hyperbranched poly(amine-ester)s as acid-sensitive drug carriers

Abstract

Novel thermo-responsive hyperbranched poly(amine-ester)s were designed and synthesized successfully in one-pot through proton-transfer polymerization of triethanolamine, trimethylolpropane, and glycidyl methacrylate with potassium hydride as a catalyst. The structure of the obtained polymers was confirmed by nuclear magnetic resonance, gel permeation chromatography, Fourier transformed infrared spectroscopy, and differential scanning calorimetery techniques. Thermal induced phase transition behaviors of hyperbranched poly(amine-ester)s were investigated by dynamic light scattering measurements, and the results indicated that these polymers had a tunable lower critical solution temperature (LCST) ranging from 37 to 57 °C. In vitro evaluation suggested that hyperbranched poly(amine-ester)s exhibited low cell cytotoxicity and efficient cell internalization against COS-7 cells. Moreover, doxorubicin (DOX) as a model drug was encapsulated into hyperbranched poly(amine-ester)s in aqueous solution above the LCST. In vitro release studies revealed that the loaded DOX displayed acid-triggered (pH ≈ 5.0) drug release behaviors. The DOX-loaded delivery system was investigated for proliferation inhibition of a Hela human cervical carcinoma cell line, and the DOX dose required for 50% cellular growth inhibition (IC₅₀) was found to be 1.1 μg mL⁻¹. All of these results suggest that thermo-responsive hyperbranched poly(amine-ester)s can be used to construct promising drug delivery systems for cancer therapy.