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载雷公藤甲素靶向制剂的制备及质量、靶向性、细胞毒性评价
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| 篇名： | 载雷公藤甲素靶向制剂的制备及质量、靶向性、细胞毒性评价 |
| TITLE： | Preparation and evaluation of quality，targeting and cytotoxicity of triptolide-loaded targeting nanoparticles |
| 摘要： | 目的 制备雷公藤甲素（TP）纳米粒子靶向制剂，并评价其质量、靶向性和细胞毒性作用。方法使用乳化挥发法，以聚乳酸-羟基乙酸共聚物/聚乙二醇/叶酸（PLGA-PEG-FA）为载体，制备载TP靶向FA受体的聚合物纳米粒子（TP@PLGA-PEG-FA），观察其形态及分布，测定其粒径、Zeta电位、多分散性指数（PDI）、载药量、包封率，评价其稳定性、血液相容性、体外释药情况、RAW264.7细胞摄取情况（以荧光染料Cy3.5定位）和体外细胞毒性。结果TP@PLGA-PEG-FA呈球形，分布均匀，粒径为（122.60±0.02）nm，Zeta电位为（－17.6±0.6）mV，PDI为0.26±0.02；TP的载药量和包封率分别为（7.78±0.05）%和（68.62±0.03）%；其在4℃水中放置14d和在37℃、含有10%胎牛血清的DMEM培养基中放置12h的粒径、PDI、Zeta电位均无明显变化。100、200、300、400µg/mLTP@PLGA-PEG-FA的溶血率分别为0.77%、0.92%、1.34%、1.63%。TP@PLGA-PEG-FA在pH5.5的磷酸盐缓冲液中72h时的累积释放量为（84.83±0.29）%，较pH7.4、6.5磷酸盐缓冲液中72h时的累积释放量[分别为（42.37±0.35）%、（63.83±0.29）%]显著升高（P＜0.05）。激活的RAW264.7细胞对Cy3.5@PLGA-PEG-FA的摄取明显多于其对Cy3.5@PLGA-PEG-FA+游离FA和Cy3.5@PLGA-PEG的摄取；当TP质量浓度≥15.63ng/mL时，TP@PLGA-PEG-FA组激活细胞的存活率显著低于同质量浓度游离TP组（P＜0.05）。结论所制备的TP@PLGA-PEG-FA稳定性高、血液相容性好，对炎症细胞具有主动靶向性和细胞毒性。 |
| ABSTRACT： | OBJECTIVE To prepare nanoparticle-based targeting preparation loaded with triptolide （TP）， and evaluate its quality， targeting ability and cytotoxic effects. METHODS Polymer nanoparticles carrying TP-targeted folic acid （FA） receptor （TP@PLGA-PEG-FA） were fabricated using poly （lactic-co-glycolic acid）/polyethylene glycol/FA （PLGA-PEG-FA） as the carrier by emulsion and volatilization technique. The morphology and distribution were observed， and their particle size， Zeta potential， polydispersity index （PDI）， drug loading capacity and encapsulation efficiency were measured. Their stability， blood compatibility， in vitro drug release， uptake by RAW264.7 cells （localization with fluorescent dye Cy3.5）， and in vitro cytotoxicity were evaluated. RESULTS TP@PLGA-PEG-FA exhibited spherical shape and uniform distribution， with particle size of （122.60±0.02） nm， Zeta potential of （－17.6±0.6）mV， and PDI of 0.26±0.02； drug loading capacity and encapsulation efficiency of TP were measured to be （7.78±0.05）% and （68.62±0.03）%， respectively. The hemolysis rates of 100， 200， 300， 400 µg/mL TP@PLGA- PEG-FA were 0.77%， 0.92%， 1.34% and 1.63%， respectively. There were no significant changes in particle size， PDI and Zeta potential when TP@PLGA-PEG-FA were placed in 4 ℃ water for 14 days and in DMEM culture medium containing 10% fetal bovine serum at 37 ℃ for 12 h. The cumulative release rate of TP@PLGA-PEG-FA was （84.83±0.29）% in phosphate buffer at pH5.5 for 72 h， which was significantly higher than the cumulative release rates in phosphate buffer solutions at pH7.4 and 6.5 for 72 h （[ 42.37±0.35）% and （63.83±0.29）% ， respectively] （P＜0.05）. Activated RAW264.7 cells took up significantly more Cy3.5@PLGA-PEG-FA than they took up Cy3.5@PLGA-PEG-FA+free FA and Cy3.5@PLGA-PEG. When the mass concentration of TP was≥15.63 ng/mL， the survival rates of activated cells in the TP@PLGA-PEG-FA groups were significantly lower than those of the same mass concentration of free TP groups （P＜0.05）. CONCLUSIONS The prepared TP@PLGA-PEG-FA has high stability， good blood compatibility， active targeting and cytotoxicity to inflammatory cells. |
| 期刊： | 2025年第36卷第12期 |
| 作者： | 尹茉莉；罗文彬；徐婧哲；唐泽波；郭妮；劳友幸；王会岩 |
| AUTHORS： | YIN Moli，LUO Wenbin，XU Jingzhe，TANG Zebo，GUO Ni，LAO Youxing，WANG Huiyan |
| 关键字： | 雷公藤甲素；类风湿关节炎；细胞毒性；靶向制剂；纳米粒子 |
| KEYWORDS： | triptolide； rheumatoid arthritis； cytotoxicity； targeting preparation； nanoparticles |
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