pH-Responsive polymeric vesicles prepared via polymerization-induced self-assembly for controlled 5-fluorouracil delivery

Abstract

Stimuli-responsive polymeric vesicles are promising nanocarriers for the controlled release of chemotherapeutic agents. Although pH-responsive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) vesicles have been widely studied for the delivery of drugs such as doxorubicin hydrochloride, their use in 5-fluorouracil (5-FU) delivery has not been reported. Here, we demonstrate for the first time the application of PDPA-based vesicles for pH-triggered release of 5-FU. The vesicles were prepared via polymerization-induced self-assembly (PISA) using reversible addition–fragmentation chain transfer (RAFT) polymerization of DPA with poly(N,N-dimethylacrylamide) (PDMA) as a macro-chain transfer agent in a water/ethanol medium. The vesicles remained stable at physiological pH but disassembled under acidic conditions due to the hydrophobic-to-hydrophilic transition of the PDPA block, resulting in accelerated release of 5-FU. Cytotoxicity assays in HCT116 cells showed comparable anticancer efficacy between vesicle-loaded and free 5-FU, while blank vesicles were nontoxic. Confocal laser scanning microscopy (CLSM) confirmed efficient cellular uptake. These results highlight PDPA-based vesicles as a novel and effective nanoplatform for pH-responsive delivery of 5-FU.