Functional polylactide- g -paclitaxel-poly(ethylene glycol) by azide-alkyne click chemistry

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 ¹H 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.