School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran.
Transport Laboratory Phenomena (TPL), Department of Food Science and Technology, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran.
Int J Biol Macromol. 2020 May 15;151:428-440. doi: 10.1016/j.ijbiomac.2020.02.141. Epub 2020 Feb 14.
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.
氧化锌纳米结构和壳聚糖（CS）固有的选择性细胞毒性、抗菌活性和独特的物理化学性质，使它们成为药物输送的有前途的候选物。在这项研究中，通过 N-琥珀酰壳聚糖功能化的氧化锌纳米粒子被用作 pH 敏感的输送系统，以增强姜黄素（CUR）的治疗潜力。通过共沉淀法在 CS 的存在下合成 CS 涂覆的 ZnO 纳米粒子。通过琥珀酸酐对 CS-ZnO 颗粒进行化学修饰，以引入-COOH 官能团，然后使用 1,1'‑碳二亚胺将其活化以用于 CUR 缀合。具有平均粒径为 40nm 的球形 CUR 缀合体系（CUR-CS-ZnO）与游离 CUR 相比表现出显著增强的水分散性。从该体系中释放 CUR 的实验研究显示出 pH 敏感的释放特性，从而能够将药物递送到肿瘤和感染部位。MTT 和 Annexin-V FITC/PI 测定表明，与游离 CUR 相比，CUR-CS-ZnO 对乳腺癌细胞（MDA-MB-231）具有更高的抗癌活性，通过诱导凋亡反应而对 HEK293 正常细胞没有细胞毒性作用。此外，CUR 与该体系的缀合显著降低了对金黄色葡萄球菌和大肠杆菌的 MIC（25 至 50 倍）和 MBC 值（10 至 40 倍）。这些特性使该制剂有资格用于未来的抗癌和抗菌应用。
