文献:Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer
文献链接:https://www.cqvip.com/doc/journal/2722693739
作者:Yang Lei; Zhang Zhenghai; Hou Jian; Jin Xin; Ke Zhongcheng; Liu Dan; Du Mei; Jia Xiaobing; Lv Huixia
相关产品:PEG-PCL聚乙二醇-聚己内酯
原文摘要:Ginsenoside compound K(CK)is one of the effective ingredients in antitumor composition of ginsenoside. However, the poor water solubility and significant efflux have limited the widespread clinical use of CK. In this study, preparation of novel CK-loaded d-alpha-tocopheryl polyethylene glycol 1,000 succinate/poly(ethylene glycol)-poly(ε-caprolactone)mixed micelles(CK-M)is discussed to solve the above problems. Particle size, zeta potential, and morphology were characterized using dynamic light scattering and transmission electron microscopy. CK-M are spherical shaped with an average particle size of 53.07±1.31 nm with high drug loading of 11.19%±0.87% and entrapment efficiency of 94.60%±1.45%. Water solubility of CK was improved to 3.78±0.09 mg/mL, which was <sup>1</sup>07.35 times higher than free CK. A549 and PC-9 cells were used to evaluate in vitro cytotoxicity and cellular uptake. IC<sub>50</sub> values of CK-M in A549 and PC-9 cells(24 h)were 25.43±2.18 and 18.35±1.90μg/mL, respectively. Enhanced cellular uptake of CK-M was observed in both cells. Moreover, CK-M promoted tumor cell apoptosis, inhibited tumor cell invasion, metastasis, and efflux through regulation of Bax, Bcl-2, matrix metalloproteinase-2, Caspase-3, and P-glycoprotein. In vivo imaging indicated that CK-M has excellent tumor targeting effect within 24 h, and the relative tumor inhibition rate of CK-M was 52.04%±4.62% compared with control group(P <0.01). Thus, CK-M could be an appropriate delivery agent for enhanced solubility and antitumor effect of CK.
PEG-PCL作为混合胶束的组成部分,与TPGS(维生素E聚乙二醇琥珀酸酯)共同构建的化合物递送系统。人参皂苷(CK)是一种从人参中提取的生物活性成分,已被证实具有antitumor activity,但由于其水溶性差以及在体内的生物利用度低,限制了其的应用。研究团队利用PEG-PCL混合微胶束作为递送系统,包裹人参皂苷化合物K,为化合物的稳定运输提供了可靠的载体。通过PEG-PCL结构,避免化合物在运输过程中被过早代谢或破坏,确保化合物能够\到达病灶部位,以提高人参皂苷(CK)的效果。
图1:装载cK的胶束的特性
PEG-PCL是一种两亲性段共聚物,具备良好的生物相容性和生物降解性。该材料在化合物递送系统中显示出其性能。通过与TPGS(聚乙烯醇-琥珀酸酯)结合,制备了PEG-PCL/TPGS混合微胶束。这种混合微胶束不仅提高了人参皂苷(CK)的溶解度,还有效增强了其在cancer cell中的摄取能力,并实现了靶向递送。
在体外实验中,PEG-PCL/TPGS混合微胶束成功将人参皂苷(CK)递送至lung carcinoma cell,从而抑制了细胞的增殖并诱导了细胞Apoptosis 。进一步的动物实验表明,该系统在降低tumor体积和转移方面也表现出效果,同时具有良好的安全性,未观察到明显的副作用。此外,PEG-PCL还能够实现对化合物的靶向递送。通过特定的修饰和设计,该混合胶束能够特异性地识别lung carcinoma cell,将化合物输送到tumor部位,提具有效果。
图2:优化后的cK-M
结论:PEG-PCL(聚乙二醇-聚己内酯)作为混合胶束的组成部分,提高了人参皂苷(CK)的靶向递送能力。PEG-PCL的稳定性和生物相容性,有效保护了化合物,延长了其在体内的循环时间。此外,PEG链所提供的亲水性促进了化合物与tumor细胞的相互作用,使有效物质能够有效地从胶束中释放,达到效果。