Chen Zhifeng, Dai Jinglun, Fu Nian, Yan Zhihong, Zheng Qinfang, Liu Yi
School of Chemistry and Chemical Engineering GDPU, Guangdong Pharmaceutical University China
School of Pharmacy GDPU, Guangdong Pharmaceutical University China.
RSC Adv. 2024 Sep 30;14(42):31210-31216. doi: 10.1039/d4ra05654j. eCollection 2024 Sep 24.
In order to enhance the water solubility of chemotherapeutic drugs, improve their biodistribution and narrow therapeutic window, two molecules of PDAO and FA-DAO with acid-sensitive Schiff base structure were designed and synthesized based on dopamine linolenate (DAO) in this paper, and subsequently drug-loaded nanoparticles were prepared by simply mixing of them with curcumin (Cur) in aqueous solution. These nanoparticles can release a large amount of the drug in response to pH changes in the tumor microenvironment through passive targeting. The cumulative rate of drug release can reach up to 70% within 24 hours under pH = 5.0 conditions as a release medium. Furthermore, the drug-carrying nanoparticles achieve active targeting through folic acid (FA) on their surface, which further enhances targeting efficiency. The inhibitory effect of drug-loaded nanoparticles was nearly 8-fold enhanced than that of its loaded Active Pharmaceutical Ingredient (API) Cur on HepG2 cell lines at the administration concentration of 6.25 μg mL. In conclusion, the nanoparticles prepared in this work improved the aqueous solubility of the loaded drug Cur, where passive targeting provided by pH-responsiveness and active targeting provided by FA endowed the loaded drug Cur with highly efficient targeting of HepG2 cell lines.
为提高化疗药物的水溶性,改善其生物分布并缩小治疗窗口,本文基于亚麻酸多巴胺(DAO)设计并合成了两个具有酸敏席夫碱结构的分子PDAO和FA-DAO,随后通过将它们与姜黄素(Cur)在水溶液中简单混合制备了载药纳米颗粒。这些纳米颗粒可通过被动靶向在肿瘤微环境的pH变化时释放大量药物。以pH = 5.0条件作为释放介质时,24小时内药物累积释放率可达70%。此外,载药纳米颗粒通过其表面的叶酸(FA)实现主动靶向,进一步提高了靶向效率。在给药浓度为6.25 μg/mL时,载药纳米颗粒对HepG2细胞系的抑制作用比其负载的活性药物成分(API)姜黄素增强了近8倍。总之,本研究制备的纳米颗粒提高了负载药物姜黄素的水溶性,其中pH响应性提供的被动靶向和FA提供的主动靶向赋予了负载药物姜黄素对HepG2细胞系的高效靶向性。