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Stimulus-responsive, controlled-release systems are of great importance in medical science and have drawn significant research attention, leading to the development of many stimulus-responsive materials over the past few decades. However, these materials are mainly designed to respond to external stimuli and ignore the key problem of the amount of drug loading. In this study, exploiting the synergistic effect of boronic esters and N -isopropylacrylamide (NIPAM) pendant, we present a copolymer as an ROS and esterase dual-stimulus responsive drug delivery system that has a drug loading of up to 6.99 wt% and an entrapment efficiency of 76.9%. This copolymer can successfully self-assemble into polymer micelles in water with a narrow distribution. Additionally, the measured CMC hinted at the good stability of the polymeric micelles in water solution, ensuing long circulation time in the body. This strategy for increasing the drug loading on the basis of stimulus response opens up a new avenue for the development of drug delivery systems.

Synthesis of high drug loading, reactive oxygen species and esterase dual-responsive polymeric micelles for drug delivery