Temperature-induced self-assembly of amphiphilic triblock terpolymers to low cytotoxic spherical and cubic structures as curcumin carriers

Abstract

In this study, self-assembly of amphiphilic thermo- and UV-sensitive block terpolymers, namely poly (methyl acrylate-b-[(7-(allyloxy)-2H-chromen-2-one)-co-(2-hydroxyethyl methacrylate(]-b-N-vinylpyrrolidone) P (MA-b-[AC-co-HEMA]-b-NVP) in water at different temperatures is studied. The synthesis of terpolymers, in three various block length for hydrophobic PMA block, is carried out by atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain-transfer (RAFT)/macromolecular design by interchange of xanthate (MADIX) polymerization. Three different critical micelle temperatures (CMT) of terpolymers are calculated via UV-VIS-NIR absorptions at 600 nm. Results of self-assembly behavior of terpolymers under CMT showed spherical micelle aggregation whereas cubic-like particles with larger particle size were self-assembled at the temperatures above CMT because of second aggregation phenomena. Additionally, UV light irradiation is used to photo-crosslinking of particles owing to presence of photo-responsive coumarin derivative of AC in the middle block. The self-assembled structures are loaded with curcumin (Cur) before and after photo-crosslinking and Cur-release behavior is investigated at different temperatures of 37 and 25 °C. Drug-release behavior of samples illustrated that cumulative Cur-release above the CMT of terpolymers is higher than under CMT due to squeezing of PVP coronas and expelling of drug molecules to outside. Moreover, cumulative release of photo-crosslinked self-assembled structures was lower than before crosslinking. The cytotoxicity of terpolymers and Cur-loaded micelles was examined through culturing on the MG-63 cells which showed high cell viability after 48 h.