Sun Xiaoxiao, Yu Dongyan, Ying Zhuoyang, Pan Chuqiao, Wang Nan, Huang Fangfang, Ling Junhong, Ouyang Xiao-Kun
School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
Pharmaceutics. 2019 Nov 7;11(11):584. doi: 10.3390/pharmaceutics11110584.
Curcumin (Cur) has anticancer activities but has poor stability, which can be improved using carrier materials. In this study, chitosan was aminated to increase the number of amino groups on its surface, modified with folic acid (FA), and then made into nanoparticles by ionic crosslinking. Owing to ion interaction, the negatively charged, non-toxic tripolyphosphate (TPP) interacted with the positively charged amino group on the aminated chitosan (AmCS) surface, producing FA-AmCS-TPP nanoparticles, which were then characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry (FT-IR), and thermogravimetric analysis (TGA). Their small particle size (175.2 ± 0.99 nm) and good surface positive potential (+42.4 mV) are beneficial for carrying antitumor drugs. We subsequently investigated whether coating of Cur by AmCS allows slow drug release by FA-AmCS-TPP nanoparticles in different pH environments, and estimated the Cur loading efficiency (EE-Cur). Our results showed that the cumulative release rate of Cur at 48 h was 56.2%, and that the EE-Cur reached 94.26 ± 0.91% with nanoparticles composed of 0.10 g AmCS, 10.0 mg FA, 10.0 mg TPP, and 15.0 mg Cur. Additionally, cytotoxicity experiments showed that the Cur/FA-AmCS-TPP nanoparticles had good targeting ability for tumor cells. Therefore, the non-toxic targeted composite nanoparticles had potential as a new antitumor agent that can overcome the limitations of Cur.
姜黄素（Cur）具有抗癌活性，但稳定性较差，可通过载体材料加以改善。本研究中，壳聚糖经胺化处理以增加其表面氨基数量，再用叶酸（FA）进行修饰，然后通过离子交联制成纳米颗粒。由于离子相互作用，带负电荷的无毒三聚磷酸钠（TPP）与胺化壳聚糖（AmCS）表面带正电荷的氨基相互作用，生成FA-AmCS-TPP纳米颗粒，随后通过扫描电子显微镜（SEM）、透射电子显微镜（TEM）、傅里叶变换红外光谱法（FT-IR）和热重分析（TGA）对其进行表征。它们的小粒径（175.2±0.99 nm）和良好的表面正电位（+42.4 mV）有利于携带抗肿瘤药物。我们随后研究了AmCS对Cur的包衣是否能使FA-AmCS-TPP纳米颗粒在不同pH环境中实现药物缓释，并估算了Cur的负载效率（EE-Cur）。我们的结果表明，Cur在48小时的累积释放率为56.2%，由0.10 g AmCS、10.0 mg FA、10.0 mg TPP和15.0 mg Cur组成的纳米颗粒的EE-Cur达到94.26±0.91%。此外，细胞毒性实验表明，Cur/FA-AmCS-TPP纳米颗粒对肿瘤细胞具有良好的靶向能力。因此，这种无毒靶向复合纳米颗粒有潜力成为一种能克服Cur局限性的新型抗肿瘤药物。
