PH-sensitive curcumin conjugated micelles for tumor triggered drug delivery

Abstract

Development of new drugs are confronted with some barriers and challenges, since these projects are mainly expensive, complex, time consuming with lack of success, there is an urgent need to reformulate the current poorly water soluble anti-cancer drugs. In this study, a new type of polymer–curcumin conjugates based on glycidyl azide polymer (GAP) was developed for cancer therapy. The copolymer was used for delivery of curcumin (CUR) as an anticancer drug to cancer cells. Our method is based on the facile conjugation of CUR to amine-containing polymeric vehicles through imine linkage bonds, which could remain stable in normal physiological condition while readily dissociate by an acidic environment and make the prodrug active to liberate its payload CUR to inhibit cell growth. The results demonstrated that fabricated amphiphilic PDCs were self-assembled into nanosized micelles in aqueous solution and the micelles showed an average size of 180 nm with a good polydispersity index. Drug release studies demonstrated that this nano-conjugate is fairly stable at physiologic environments but prone to mild acidic conditions which would trigger the release of conjugated CUR. Moreover, the PDCs micelles exhibited excellent cytotoxicity effect on 4T1 mouse breast cancer cell line but no significant toxicity was observed for the copolymer. In addition, the copolymer did not display remarkable toxicity against A. salina even at high doses of copolymer. In addition, the synthesized PDCs exhibited hemolysis lowers than 6%. The safety of copolymers as a drug vehicle was also confirmed by LD50, since all mice which treated with 5000 mg/Kg (limited dose) were still alive after one week. Our findings revealed that these unique pH-sensitive PDCs may provide a promising approach for delivery of the anticancer drugs to cancer cells.