Preparation,Characterization And Multidrug Resistance Reversal Activity Of Pegylated Doxorubicin Micelles Loaded With Curcumin

Doxorubicin(DOX)is one of the most used anti-tumor drugs.Previous studies have shown that DOX is a universal anticancer agent capable of suppressing many kinds of cancers,including acute leukemia,malignant lymphoma,breast cancer,lung cancer,ovarian cancer and bladder cancer,by interfering with RNA and DNA synthesis and inducing tumor cell apoptosis.Despite these advantages,its application in anti-tumor therapy has been limited by its serious side effects and MDR.To overcome these problems,mPEG-CA-DOX,mPEG-SA-DOX and FA-PEG-SA-DOX conjugates were synthesized and their CUR-loading micelles were constructed for study of reversing MDR.Firstly,mPEG-CA-DOX,mPEG-SA-DOX and FA-PEG-SA-DOX conjugates were synthesized successfully and characterized by NMR.Secondly,mPEG-CA-DOX,mPEG-SA-DOX and FA-PEG-SA-DOX micelles and their drug-loading micelles were prepared by a solid dispersion/ultrasonic method and characterized in terms of average size,drug loading content,encapsulation efficiency and etc.These micelles have average sizes of less than 100 nm and were monodisperse(PDI <0.290).The curcumin loadings were all above 7.48% and the encapsulation efficiencies of these micelles were over 44.85%.Also,the in vitro drug release studies of mPEG-SA-DOX micelles and CUR/FA-PEG-SA-DOX micelles showed a characteristic of pH-senstive.Finally,MCF-7 and MCF-7/ADR cells were chosen to evaluate the conjugates and micelles at the cellular level.In vitro,the conjugates showed significant cytotoxicity decrease in MCF-7 cells but increase in MCF-7/ADR cells.The cytotoxicity study of micelles indicated a certain extent of synergistic anti-tumor effect.Cellular uptake and efflux study showed that folate-mediated tumor targeting effect can increase the DOX amount in micelles.