Advanced Polymer Materials Group, University Politehnica of Bucharest, 1-7 Gh Polizu Street, 011061 Bucharest, Romania.
Microbiology Immunology Department, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania; Research Institute of the University of Bucharest, 050095 Bucharest, Romania.
Colloids Surf B Biointerfaces. 2022 May;213:112423. doi: 10.1016/j.colsurfb.2022.112423. Epub 2022 Feb 23.
This work pledge to extend the therapeutic windows of hybrid nanoparticulate systems by engineering mannose-decorated hybrid nanoparticles based on poly lactic-co-glycolic acid (PLGA) and vegetable oil for efficient delivery of two lipophilic anti-inflammatory therapeutics (Celecoxib-CL and Indomethacin-IMC) to macrophages. The mannose surface modification of nanoparticles is achieved via O-palmitoyl-mannose spacer during the emulsification and nanoparticles assembly process. The impact of targeting motif on the hydrodynamic features (R, PdI), stability (ζ-potential), drug encapsulation efficiency (DEE) is thoroughly investigated. Besides, the in vitro biocompatibility (MTT, LDH) and susceptibility of mannose-decorated formulations to macrophage as well their immunomodulatory activity (ELISA) are also evaluated. The monomodal distributed mannose-decorated nanoparticles are in the range of nanometric size (R < 115 nm) with PdI < 0.20 and good encapsulation efficiency (DEE = 46.15% for CL and 76.20% for IMC). The quantitative investigation of macrophage uptake shows a 2-fold increase in fluorescence (RFU) of cells treated with mannose-decorated formulations as compared to non-decorated ones (p < 0.001) suggesting an enhanced cell uptake respectively improved macrophage targeting while the results of ELISA experiments suggest the potential immunomodulatory properties of the designed mannose-decorated hybrid formulations.
这项工作旨在通过工程化基于聚乳酸-共-羟基乙酸（PLGA）和植物油的甘露糖修饰的杂化纳米粒子，来延长杂化纳米颗粒系统的治疗窗口，以有效递送至巨噬细胞两种亲脂性抗炎治疗药物（塞来昔布-CL 和吲哚美辛-IMC）。纳米粒子的甘露糖表面修饰是通过乳化和纳米粒子组装过程中的 O-棕榈酰甘露糖间隔基来实现的。靶向基序对水动力特性（R、PdI）、稳定性（ζ-电位）、药物包封效率（DEE）的影响进行了深入研究。此外，还评估了甘露糖修饰配方对巨噬细胞的体外生物相容性（MTT、LDH）和敏感性及其免疫调节活性（ELISA）。单模态分布的甘露糖修饰纳米粒子的粒径在纳米级范围内（R < 115nm），PdI < 0.20，包封效率良好（CL 的 DEE = 46.15%，IMC 的 DEE = 76.20%）。巨噬细胞摄取的定量研究表明，与未修饰的制剂相比，用甘露糖修饰的制剂处理的细胞的荧光（RFU）增加了 2 倍（p < 0.001），这表明细胞摄取增强，分别改善了巨噬细胞靶向性，而 ELISA 实验的结果表明设计的甘露糖修饰杂化制剂具有潜在的免疫调节特性。
