Curcumin-loaded pH-sensitive carboxymethyl chitosan nanoparticles for the treatment of liver cancer

作者：Xinyu Yang, Dongdong Meng, Ning Jiang, Chaoxing Wang, Jinbo Zhang, Yanqiu Hu, Jiaming Lun, Rui Jia, Xueyun Zhang, Weitong Sun · 发表于：Journal of Biomaterials Science Polymer Edition · 年份：2024 · DOI：10.1080/09205063.2024.2304949 · 被引用次数：14 · 研究领域：Nanoparticle-Based Drug Delivery、Curcumin's Biomedical Applications、Dendrimers and Hyperbranched Polymers

In this study, the pH-responsive API-CMCS-SA (ACS) polymeric nanoparticles (NPs) based on 1-(3-amino-propyl) imidazole (API), stearic acid (SA), and carboxymethyl chitosan (CMCS) were fabricated for the effective transport of curcumin (CUR) in liver cancer. CUR-ACS-NPs with various degrees of substitution (DS) were employed to prepare through ultrasonic dispersion method. The effect of different DS on NPs formation was discussed. The obtained CUR-ACS-NPs (DSSA=12.4%) had high encapsulation rate (more than 85%) and uniform particle size (186.2 ± 1.42 nm). The CUR-ACS-NPs showed better stability than the other groups. Drug release from the CUR-ACS-NPs was pH-dependent, and more than 90% or 65% of CUR was released in 48 h in weakly acid medium (pH 5.0 or 6.0, respectively). Additionally, the CUR-ACS-NPs increased the intracellular accumulation of CUR and demonstrated high anticancer effect on HepG2 cells compared with the other groups. CUR-ACS-NPs prolonged the retention time of the drug, and the area under the curve (AUC) increased significantly in vivo. The in vivo antitumor study further revealed that the CUR-ACS-NPs exhibited the capability of inhibiting tumor growth and lower systemic toxicity. Meanwhile, CUR, CUR-CS-NPs, and CUR-ACS-NPs could be detected in the evaluated organs, including tumor, liver, spleen, lung, heart, and kidney in distribution studies. Among them, CUR-ACS-NPs reached the maximum concentration at the tumor site, indicating the tumor-targeting properti...