Functional Polylactide-<i>g</i>-Paclitaxel–Poly(ethylene glycol) by Azide–Alkyne Click Chemistry

Abstract

Functional polylactide- g -paclitaxel–poly(ethylene glycol), a novel graft polymer–drug conjugate (GPDC) with paclitaxel (PTXL) as the divalent agent to bridge between the degradable polylactide (PLA)-based backbone and hydrophilic poly(ethylene glycol) (PEG) side chains, were prepared by the copper-catalyzed azide–alkyne cycloaddition reaction of acetylene-functionalized polylactide (PLA) with azide-functionalized PTXL–PEG conjugate. The acetylene-functionalized PLA was prepared by ring-opening copolymerization (ROCP) of acetylene-functionalized LA monomer with l -lactide (LA). The azide-functionalized PTXL–PEG conjugate was prepared by multistep organic synthesis. The well-controlled chemical structures of the GPDC and its precursors were verified by 1 H NMR and GPC characterizations. DLS analysis indicated that GPDC molecules assembled in water to form nanoparticles with sizes of 8–40 nm. GPC analysis of buffer solutions (pH = 5.5 and 7.4) of the GPDC suggested the occurrence of multiple hydrolysis reactions under the experimental conditions, which resulted in the release of PTXL moieties and the cleavage of PLA-based backbone.