Stimuli-responsive And Interfacial Crosslinked Polymer Micelle As Drug Delivery

Drug delivery, especially anticancer drug delivery systems have occupiedwidespread attention for enhancing drug efficacy and reducing undesirable sideeffects. Polymer micelles with specific advantages such as facile modification andmanufacturing are considered as one of the most promising nanocarrier systems foranticancer drugs. In recent years,“intelligent” drug carriers, that exhibit stimuli-responsive behavior in response to an external signal, are spotlighted in research ofselective controlled-release.In this study, a polymer micelle system as vehicle or the delivery of DOX hasbeen developed. The device was designed with a pH-responsive charge-conversionalproperty and reductive responsive through reductive cleavage of the interfacialdisulfide bonds. Ring opening polymerizationg and RAFT polymerization wereconmbined to prepare amphiphilic block copolymer PCL₃₆–P [PEGMEA₁₂-（APMAa₅-DMMA₅）]. The2,3-dimethylmaleic anhydride （DMMA） conjugated copolymer self-assembled into core-shell structured micelle in phosphate buffer （pH7.4）.Surfacecharge of the aggregates was reversed from negative to positive at acidic environment（pH6.5）. Cellular uptake of DOX-nanoparticles （DOX-NP_s） was greatly enhanced inan acidic pH condition due to the surface charge reversal. Further stabilization of themicellar system was performed via RAFT polymerization using a disulfide cross-linker to cross-link the self-assemblies. The interface-cross-linked micelle was foundto present better properties than the non-crosslinked block copolymer micelle duringthe drug loading and releasing experiment. Both block copolymers and cross-linkedmicelles show low toxicity on L929cells.