The purpose of this study is to design and develop thermoresponsive nano-sized hydrogel particles from a natural polymer, chitosan, as smart material platforms for curcumin delivery. Chitosan was used as the backbone material to be grafted with poly–(N-isopropylacrylamide) (pNIPAM) using an EDC/NHS coupling reaction. The conjugated products were characterized by ¹H NMR and TGA. Chitosan-grafted pNIPAM (CS-g-pN) nanogels were prepared by a sonication method. The loading of curcumin into the CS-g-pN nanogels was achieved using an incubation method. Size, morphology of nanogels, amounts of curcumin loaded to the nanogels and cellular uptake were investigated by DLS, TEM, fluorescent spectroscopy and confocal microscopy techniques, respectively. A CellTiter-Blue^® cell viability assay was performed in NIH-3T3 and HeLa cells to assess the safety while MTT assay was carried out in MDA-231, Caco-2, HepG2, and HT-29 cells for determining cytotoxic effects. Results showed that CS-g-pN with 3–60% degree of modification were simply assembled into spherical nanogel particles with submicron sizes, in which curcumin was encapsulated. The thermoresponsive behavior of each CS-g-pN nanogel formulation differed due to the grafted pNIPAM length and density. The CS-g-pN nanogel formulations were non-toxic towards NIH-3T3 and HeLa cells. Each curcumin-loaded CS-g-pN nanogel formulation could be up taken into NIH-3T3 cell lines and showed the dose-dependent cytotoxicity against tested cell lines. Successful development of this curcumin-loaded nanogel will lead to advanced materials that can be functionalized and optimized for targeted therapy and controlled delivery of small molecules and/or biomolecules for biomedical applications.

这项研究的目的是设计和开发天然聚合物壳聚糖的热响应性纳米尺寸水凝胶颗粒，作为姜黄素输送的智能材料平台。壳聚糖被用作通过EDC / NHS偶联反应接枝聚N-异丙基丙烯酰胺（pNIPAM）的骨架材料。共轭产物通过¹ H NMR和TGA表征。通过超声处理制备了壳聚糖接枝的pNIPAM（CS-g-pN）纳米凝胶。使用孵育方法将姜黄素加载到CS-g-pN纳米凝胶中。分别通过DLS，TEM，荧光光谱和共聚焦显微镜技术研究了纳米凝胶的尺寸，形态，姜黄素的负载量和细胞摄取。一的CellTiter蓝^®在NIH-3T3和HeLa细胞中进行细胞活力测定以评估安全性，而在MDA-231，Caco-2，HepG2和HT-29细胞中进行MTT测定以确定细胞毒性作用。结果表明，具有3–60％修饰度的CS-g-pN可以简单地组装成亚微米尺寸的球形纳米凝胶颗粒，其中封装了姜黄素。每个CS-g-pN纳米凝胶制剂的热响应行为由于接枝的pNIPAM长度和密度而有所不同。CS-g-pN纳米凝胶制剂对NIH-3T3和HeLa细胞无毒。每种姜黄素负载的CS-g-pN纳米凝胶制剂均可吸收到NIH-3T3细胞系中，并显示出对测试细胞系的剂量依赖性细胞毒性。