| 余梦诗,罗青清.聚乳酸-羟基乙酸共聚物纳米粒在孕鼠中应用的安全性及靶向性评价[J].安徽医药,待发表. |
| 聚乳酸-羟基乙酸共聚物纳米粒在孕鼠中应用的安全性及靶向性评价 |
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| 投稿时间：2025-05-20 录用日期：2025-06-24 |
| DOI： |
| 中文关键词: 纳米颗粒 靶向作用 聚乳酸-羟基乙酸共聚物 妊娠期 安全性 |
| 英文关键词: |
| 基金项目:四川省自然科学基金项目(编号:2022NSFSC1373),项目负责人:罗青清；古蔺县人民医院-西南医科大学附属医院科技战略合作项目(编号:2022GLXNYDFY07),项目负责人:罗青清。 |
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| 中文摘要: |
| 目的:构建聚乳酸-羟基乙酸共聚物(poly(lactic-co-glycolic acid), PLGA)纳米粒,在孕鼠体内运用探讨其在孕期应用的安全性及靶向性。方法:采用乳液溶剂挥发法制备搭载荧光标记的不同形状PLGA纳米粒,通过动态光散射技术测定纳米粒粒径大小和多分散性指数(Polymer dispersity index, PDI),采用扫描电子显微镜观察纳米粒的表面形貌与结构,采用紫外分光光度法测定纳米粒对荧光探针的装载率(Loading Efficiency, LE)及包封率(Encapsulation Efficiency, EE)。通过鼠尾静脉注射不同形状PLGA纳米粒至孕鼠体内,检测其在孕鼠主要脏器、胎盘以及胎鼠的荧光分布情况,评价纳米粒的靶向性能。通过对孕鼠肝、肾、胎盘等重要器官进行苏木精-伊红染色观察,评价PLGA纳米粒对孕鼠的安全性。结果:球形PLGA纳米粒(Spherical nanoparticles, NSs)的平均粒径为200.30±3.49 nm,PDI=0.05±0.01,其尺寸小、粒径均一,具有光滑的球形形貌；棒状PLGA纳米粒(Rod nanoparticles, NRs)长径为583.37±197.43 nm,短径为89.37±25.12 nm,具有典型的棒状结构。NSs对荧光染料的LE为0.41±0.02%,EE为41.41±2.02%,NRs对荧光染料的LE为0.49±0.03%,EE为49.49±3.02%。NSs与NRs均能靶向胎盘,其中NSs具有更良好的胎盘靶向性,并且不会通过胎盘蓄积于胎鼠,也不会损伤孕鼠重要脏器。结论:通过乳液溶剂挥发法制备的不同形状PLGA纳米粒均可靶向胎盘,其中NSs胎盘靶向性及母婴安全性均高于NRs,具有作为治疗妊娠期相关疾病药物载体的潜力。 |
| 英文摘要: |
| Objective: To construct nanoparticles suitable for use in pregnant mice and investigate their safety and targeting ability during pregnancy.Methods: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles of different shapes were prepared by emulsion solvent volatilization and fluorescently labeled to study their targeting performance in pregnant mice. The surface morphology of nanoparticles was characterized, the size and polymer dispersity index (PDI) of nanoparticles were determined by dynamic light scattering (DLS), the surface morphology and structure of nanoparticles were observed by scanning electron microscopy, and the loading efficiency of nanoparticles on fluorescent probes was determined by ultraviolet spectrophotometry. LE) and Encapsulation Efficiency (EE). PLGA nanoparticles of different shapes were applied to pregnant mice by intravenous administration of rat tail, and the fluorescence distribution of PLGA nanoparticles in the main organs, placenta and fetal mice of pregnant mice was detected, and the targeting performance of nanoparticles was evaluated. The safety of PLGA nanoparticles in pregnant mice was evaluated by hematoxylin-eosin (H E) staining of liver, kidney, placenta and other important organs of pregnant mice. Results: The average particle size of spherical PLGA nanoparticles NSs was 200.30±3.49 nm, PDI=0.05±0.01, and their size was small, the particle size was uniform, and the spherical morphology was smooth. The rod-shaped PLGA nanoparticles have a typical rod-like structure with a long diameter of 583.37±197.43 nm and a short diameter of 89.37±25.12 nm. The LE of NSs for fluorescent dyes was 0.41±0.02%, EE was 41.41±2.02%, and the LE of NRs for fluorescent dyes was 0.49±0.03%, and EE was 49.49±3.02%. Both NSs and NRs can target the placenta, and NSs have better placental targeting, and will not accumulate in fetal mice through the placenta, nor will they damage the important organs of pregnant mice. Conclusion: PLGA nanoparticles of different shapes prepared by emulsion solvent volatilization can target the placenta, and the targeting and maternal and infant safety of NSs are higher than those of NRs, and they have the potential to be used as drug carriers for the treatment of pregnancy-related diseases. |
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