A pH and UCST thermo-responsive tri-block copolymer (PAA-b-PDMA-b-P(AM-co-AN)) with micellization and gelatinization in aqueous media for drug release

Abstract

A brand new pH and thermo-responsive amphiphilic ABC triblock copolymer of poly(acrylic acid)-block-poly(N,N-dimethyl acrylamide)-block-poly(acrylamide-co-acrylonitrile) (PAA-b-PDMA-b-P(AM-co-AN)) was synthesized via sequential reversible addition–fragmentation chain transfer (RAFT) polymerization. Due to the pH-responsive blocks of PAA and thermo-responsive blocks of P(AM-co-AN), the properties of the copolymer solution were controlled by varying parameters such as temperature and pH. Specifically, it formed different nanostructures and showed gel behavior under different conditions. In detail, under high temperature alkaline conditions, ADAA was dissolved in an aqueous solution in the form of a molecular chain. Thereafter, when the temperature became lower or pH became acidic, the triblock copolymer self-assembled into different micelle structures, including shell–core, core–shell–core and tighter core–linking–core nanoparticles. In addition, the phase transition temperature of the copolymer was adjusted by pH and concentration. When the copolymer hydrogel was injected into a simulated human body device, it showed sustained drug release behavior and low transient drug concentrations. MTT experiments demonstrated the good biocompatibility of the ADAA hydrogels. This research provides inspiration to develop new polymers which are expected to be promising candidates as part of drug delivery platforms. Compared with traditional responsive hydrogels, its UCST can be easily controlled and is more stable through the feeding ratio, making it more advantageous in human drug delivery applications. In summary, we believe that this UCST and pH-responsive injectable ADAA hydrogel is researchable and applicable in the biomedical field.