Synthesis and characterization of a pH- and enzyme-sensitive poly(ethylene glycol)-hyaluronic acid-melphalan prodrug

Prodrug development is an important strategy for improving tumor cell targeting and the selectivity of anticancer drugs. In this study, poly(ethylene glycol) and melphalan, an anticancer drug, were linked to the backbone of hyaluronic acid via amide bonds using carbodiimide chemistry to synthesize a poly(ethylene glycol)–hyaluronic acid–melphalan prodrug. The physicochemical properties of the prodrug were characterized by Fourier transform infrared, proton nuclear magnetic resonance, ultraviolet–visible spectroscopy, and dynamic light scattering and transmission electron microscopy. The in vitro drug release profiles and the corresponding in vitro cell evaluation of the prodrug were investigated. The poly(ethylene glycol)–hyaluronic acid–melphalan prodrug was successfully synthesized and self-assembled into 116.4-nm nanoparticles. The release profiles demonstrated that controlled release of the prodrug could be achieved with a sensitive property involving both pH and enzymatic degradation. The poly(ethyle...