Xv Liuli, Qian Xinxin, Wang Yan, Yu Chenghuan, Qin Dingkui, Zhang Yahui, Jin Peng, Du Qizhen
The Key Laboratory for Quality Improvement of Agricultural Products of Zhejiang Province, College of Agricultural and Food Sciences, Zhejiang A & F University, Hangzhou 311300, China.
Experimental Animal Center of the Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
Nanomaterials (Basel). 2020 Mar 2;10(3):451. doi: 10.3390/nano10030451.
This study aims to stabilize loaded celecoxib (CX) by modifying the structure of casein nanoparticles through phosphatidylcholine. The results show that Egg yolk phosphatidylcholine PC (PC) significantly increased the stability of CX-PC-casein nanoparticles (NPs) (192.6 nm) from 5 min (CX-β-casein-NPs) to 2.5 h at 37 °C. In addition, the resuspended freeze-dried NPs (202.4 nm) remained stable for 2.5 h. Scanning electron microscopy indicated that PC may block the micropore structures in nanoparticles by ultrasonic treatment and hence improve the physicochemical stability of CX-PC-casein-NPs. The stability of the NPs was positively correlated with their inhibiting ability for human malignant melanoma A375 cells. The structural modification of CX-PC-casein-NPs resulted in an increased intracellular uptake of CX by 2.4 times than that of the unmodified ones. The pharmacokinetic study showed that the Area Under Curve (AUC) of the CX-PC-casein-NPs was 2.9-fold higher in rats than that of the original casein nanoparticles. When CX-PC-casein-NPs were intravenously administrated to mice implanted with A375 tumors (CX dose = 16 mg/kg bodyweight), the tumor inhibition rate reached 56.2%, which was comparable to that of paclitaxel (57.3%) at a dose of 4 mg/kg bodyweight. Our results confirm that the structural modification of CX-PC-casein-NPs can effectively prolong the remaining time of specific drugs, and may provide a potential strategy for cancer treatment.
本研究旨在通过磷脂酰胆碱修饰酪蛋白纳米颗粒的结构来稳定负载的塞来昔布（CX）。结果表明，蛋黄磷脂酰胆碱PC显著提高了CX-PC-酪蛋白纳米颗粒（NPs）（192.6 nm）在37℃下的稳定性，从5分钟（CX-β-酪蛋白-NPs）延长至2.5小时。此外，重新悬浮的冻干纳米颗粒（202.4 nm）在2.5小时内保持稳定。扫描电子显微镜表明，PC可能通过超声处理封闭纳米颗粒中的微孔结构，从而提高CX-PC-酪蛋白-NPs的物理化学稳定性。纳米颗粒的稳定性与其对人恶性黑色素瘤A375细胞的抑制能力呈正相关。CX-PC-酪蛋白-NPs的结构修饰导致CX的细胞内摄取量比未修饰的纳米颗粒增加了2.4倍。药代动力学研究表明，CX-PC-酪蛋白-NPs在大鼠体内的曲线下面积（AUC）比原始酪蛋白纳米颗粒高2.9倍。当将CX-PC-酪蛋白-NPs静脉注射给植入A375肿瘤的小鼠（CX剂量=16 mg/kg体重）时，肿瘤抑制率达到56.2%，与剂量为4 mg/kg体重的紫杉醇（57.3%）相当。我们的结果证实，CX-PC-酪蛋白-NPs的结构修饰可以有效延长特定药物的留存时间，并可能为癌症治疗提供一种潜在策略。
