Preparation And Characterization Of Redox-sensitive Polymer-curcumin Conjugate Micelles

Redox-sensitive disulfide bond(-SS-) was introduced to the curcumin(Cur) to give a curcumin derivative(Cur-SS-COOH) in this research. Then Cur-SS-COOH reacted with biodegradable amphiphilic polymer methoxy poly(ethylene glycol)-poly(lactic acid) copolymer(mPEG-PLA) to afford the redox-sensitive polymer-drug conjugate(mPEG-PLA-SS-Cur). And then the polymeric conjugate micelles were prepared by a typical dialysis method. Meanwhile, non-redox-sensitive polymer-drug conjugate(mPEG-PLA-Cur) was also successfully synthesized, and the non-redox-sensitive curcumin micelle was prepared by dialysis method, too.The structures of both monomers were confirmed by 1H NMR and 13 C NMR. The curcumin graft ratio of mPEG-PLA-SS-Cur and mPEG-PLA-Cur were 89% and 66% respectively according to the peak area of 1H NMR. The critical micelle concentrations(CMC) were 6.74 ± 0.36 and 7.13 ± 0.94 ?g/mL respectively, so both micelles have a very good stability. The size of mPEG-PLA-SS-Cur and mPEG-PLA-Cur were 115.60 ± 5.89 and 102.87 ± 2.50 nm characterized by DLS. The morphology of two kinds of micelles were spherical and uniformly distributed, which is conducive to passive targeting effect. The drug loading of two micelles were 8.22%(mPEG-PLA-SS-Cur) and 5.81%(mPEG-PLA-Cur) calculated according to the peak area of 1H NMR.The drug release study showed that the cumulative drug release rate of the redox-sensitive micelles(mPEG-PLA-SS-Cur) was significantly higher than the non-redox-sensitive micelles(mPEG-PLA-Cur) at pH 7.4, containing 10 mM DTT, which fully proved the redox-sensitive character of the disulfide bond, and demonstrated that the redox environment could trigger a rapid release of curcumin.We also conducted cell viability assay and cellular uptake experiments on HeLa cells. The results showed that compared with the non-redox-sensitive micelles(mPEG-PLA-Cur) the redox-sensitive micelles(mPEG-PLA-SS-Cur) had a greater cytotoxicity and cellular uptake ability.In conclusion, the redox-sensitive curcumin micelles are expected to become a carrier for controlled release of anti-cancer drugs, and have a broad prospect in the application of anticancer drug delivery system.