Abstract
Inherent selective cytotoxicity, antibacterial activity and unique physicochemical properties of ZnO nanostructures and chitosan (CS) make them promising candidates for drug delivery. In this study, ZnO nanoparticles functionalized by N-succinyl chitosan as a pH-sensitive delivery system were synthesized to enhance the therapeutic potential of curcumin (CUR). CS coated-ZnO nanoparticles were synthesized by a co-precipitation method in the presence of CS. Chemical modification of CS-ZnO particles was performed by succinic anhydride for introducing –COOH functional groups which were then activated using 1,1′‑carbonyldiimidazole for CUR conjugation. The spherical-like CUR-conjugated system (CUR-CS-ZnO) with the average particle size of 40 nm presented significantly enhanced water dispersibility versus free CUR. The experimental study of CUR release from the system showed a pH-sensitive release profile, which enabled drug delivery to tumors and infection sites. MTT and Annexin-V FITC/PI assays revealed the superior anticancer activity of CUR-CS-ZnO compared to free CUR against breast cancer cells (MDA-MB-231) by inducing the apoptotic response with no cytotoxic effects on HEK293 normal cells. Moreover, CUR conjugation to the system notably dropped the MIC (25 to 50-fold) and MBC values (10 to 40-fold) against S. aureus and E. coli. The features qualify the formulation for anticancer and antimicrobial applications in the future.
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