载姜黄素的透明质酸-熊果酸-硫辛酸交联纳米粒的制备及其体外抗肿瘤活性

目的 制备载姜黄素的透明质酸-熊果酸-硫辛酸交联纳米粒（Cur/cLA-HU NPs），并进行体外抗肿瘤活性评价。方法 以载药量、包封率为指标，采用超声法，通过单因素考察优化Cur/cLA-HU NPs的制备工艺，并对Cur/cLA-HU NPs的粒径、Zeta电位、形态和体外释药情况进行评价。通过荧光倒置显微镜分析HepG2细胞对Cur/cLA-HU NPs的摄取，以MTT法考察Cur/cLA-HU NPs对HepG2细胞的毒性。结果 最佳载药工艺为：以甲醇为药物姜黄素有机溶剂，以药质比4∶10进行投料，超声于100 W下次数为3次，每次处理3 min，超声程序设置为开2 s、停4 s。Cur/cLA-HU NPs的包封率为（87.91±1.51）%，载药量为（16.64±0.45）%，粒径为（172.3±2.57）nm，PDI为（0.174±0.021），分散均匀，Zeta电位为（−35.3±2.12）mV。Cur/cLA-HU NPs具有还原响应性，释放药物的快慢受到GSH浓度的影响；靶向肿瘤细胞，且被细胞快速摄取；对HepG2人肝癌细胞增殖具有明显抑制作用。结论 Cur/cLA-HU NPs载药量和包封率高，其体外抗肿瘤活性稍优于姜黄素，具有肿瘤靶向性。

Preparation of curcumin-loaded hyaluronic acid-ursolic acid-lipoic acid cross- linked nanoparticles and their antitumor activity in vitro

Objective To prepare curcumin-loaded hyaluronic acid-ursolic acid-lipoic acid cross-linked nanoparticles (Cur/cLA-HU NPs), and evaluate their antitumor activities in vitro. Methods The preparation process of Cur/cLA-HU NPs was optimized by single-factor method and verification by ultrasound, taking drug load and encapsulation rate as indicators. The particle size, Zeta potential, morphology and in vitro drug release of Cur/cLA-HU NPs were evaluated. The uptake of Cur/cLA-HU NPs by HepG2 cells was qualitatively analyzed by fluorescence inverted microscopy and the cytotoxicity of Cur/cLA-HU NPs to HepG2 cells was investigated by MTT assay. Results The optimal preparation process is as following:methanol was used as the organic solvent of curcumin, the drug mass ratio was 4:10, the number of times of ultrasonic treatment was 3 at 100 W, and each time was treated for 3 min. The ultrasonic program was set to open for 2 s and stop for 4 s. The encapsulation efficiency of Cur/cLA-HU NPs was (87.91 ±1.51)%, drug loading was (16.64 ±0.45)%, particle size was (172.3 ±2.57) nm, PDI was (0.174 ±0.021), dispersion was uniform, and Zeta potential was (−35.3 ±2.12) mV. Cur/cLA-HU NPs exhibit reduction responsiveness, and the speed of drug release was influenced by the concentration of GSH. Cur/cLA-HU NPs target tumor cells and were rapidly up-taken by cells, and had a significant inhibitory effect on the proliferation of HepG2 cells. Conclusion Cur/cLA-HU NPs have high drug load and encapsulation rate, and its anti-tumor activity in vitro is slightly better than curcumin, with tumor targeting.