Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Ministry of Education, 24 Heping Road, Xiangfang District, Harbin, Heilongjiang Province, China.
J Biomater Appl. 2024 Oct;39(4):317-331. doi: 10.1177/08853282241258161. Epub 2024 Jul 20.
Cancer is a serious threat to human life, health and social development. In recent years, nanomicelles, as an emerging drug carrier material, have gradually entered people's field of vision because of their advantages of improving bioavailability, maintaining drug levels, reducing systemic side effects and increasing drug accumulation at target sites. In this study, B-GPSG nano-micelles were prepared by film dispersion hydration method using brucine as model drug and glycyrrhetinic acid-polyethylene glycol-3-methylene glycol-dithiodipropionic acid-glycerol monostearate polymer as nano-carrier. The preparation process, characterization, drug release in vitro, pharmacokinetics and liver targeting were investigated. The results showed that the range of particle size, polydispersion index and Zeta potential were 102.7 ± 1.09 nm, 0.201 ± 0.02 and -24.5 ± 0.19 mV respectively. The entrapment efficiency and drug loading were 83.79 ± 2.13% and 12.56 ± 0.09%, respectively. The drug release experiments in vitro and pharmacokinetic experiments showed that it had obvious sustained release effect. For pharmacokinetics study, it shows that both the B-GPSG solution group and the B-PSG solution group changed the metabolic kinetic parameters of brucine, but the B-GPSG solution group had a better effect. Compared with the B-PSG solution group, the drug was more prolonged in rats. The half-life in the body and the retention time in the body of B-GPSG are more helpful to improve the bioavailability of the drug and play a long-term effect. The tail vein injection results of mice indicate that B-GPSG can target and accumulate brucine in the liver without affecting other key organs. Cell uptake experiments and tissue distribution experiments in vivo show that glycyrrhetinic acid modified nano-micelles can increase the accumulation of brucine in hepatocytes, has a good liver targeting effect, and can be used as a new preparation for the treatment of liver cancer. The B-SPSG prepared in this experiment can provide a new treatment method and research idea for the treatment of liver cancer.
癌症是对人类生命、健康和社会发展的严重威胁。近年来，纳米胶束作为一种新兴的药物载体材料，因其提高生物利用度、维持药物水平、减少全身副作用和增加药物在靶部位积累的优势，逐渐引起人们的关注。本研究以马钱子碱为模型药物，以甘草次酸-聚乙二醇-3-亚甲基二醇-二硫代二丙酸-甘油单硬脂酸酯聚合物为纳米载体，采用薄膜分散水化法制备 B-GPSG 纳米胶束，考察了其制备工艺、表征、体外释药、药代动力学及肝靶向性。结果表明，粒径、多分散指数和 Zeta 电位范围分别为 102.7±1.09nm、0.201±0.02 和-24.5±0.19mV；包封率和载药量分别为 83.79%±2.13%和 12.56%±0.09%；体外释药实验和药代动力学实验表明，其具有明显的缓释效果。药代动力学研究表明，B-GPSG 溶液组和 B-PSG 溶液组均改变了马钱子碱的代谢动力学参数，但 B-GPSG 溶液组效果更好。与 B-PSG 溶液组相比，药物在大鼠体内的半衰期和体内滞留时间更长，更有利于提高药物的生物利用度，发挥长效作用。小鼠尾静脉注射结果表明，B-GPSG 可以靶向并在肝脏蓄积马钱子碱，而不影响其他关键器官。体内细胞摄取实验和组织分布实验表明，甘草次酸修饰纳米胶束可以增加马钱子碱在肝细胞中的蓄积，具有良好的肝靶向作用，可作为治疗肝癌的新制剂。本实验制备的 B-SPSG 可为肝癌的治疗提供新的治疗方法和研究思路。
