Nanoparticles exhibit distinct behaviours within the body, depending on their physicochemical properties and administration routes. However, in vivo behaviour of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, especially when administered nasally, remains unexplored; furthermore, there is a lack of comparative analysis of uptake efficiency among different administration routes. Therefore, here, we aimed to comprehensively investigate the real-time in vivo behaviour of PLGA nanoparticles across various administration routes. PLGA-NH2 nanoparticles of three sizes were synthesised using an oil-in-water single-emulsion method. We assessed their uptake by murine macrophage RAW264.7 cells using fluorescence microscopy. To enable real-time tracking, we conjugated p-SCN-Bn-deferoxamine to PLGA-NH2 nanoparticles and further radiolabelled them with 89Zr-oxalate before administration to mice via different routes. Nanoparticle internalisation by lung immune cells was monitored using fluorescence-activated cell sorting analysis. The nanoparticle sizes were 294 ± 2.1 (small), 522.5 ± 5.58 (intermediate), and 850 ± 18.52 nm (large). Fluorescent labelling did not significantly alter the nanoparticle size and charge. The level of uptake of small and large nanoparticles by RAW264.7 cells was similar, with phagocytosis inhibition primarily reducing the internalisation of large particles. Positron emission tomography revealed that intranasal delivery resulted in the highest and most targeted pulmonary uptake, whereas intravenous administration led to accumulation mainly in the liver and spleen. Nasal delivery of large nanoparticles resulted in enhanced uptake by myeloid immune cells relative to lymphoid cells, whereas dendritic cell uptake initially peaked but declined over time. Our study provides valuable insights into advancing nanomedicine and drug delivery, with the potential for expanding the clinical applications of nanoparticles.

中文翻译：

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鼻内给药增强聚（乳酸-乙醇酸）纳米颗粒的大小依赖性肺部吞噬细胞摄取

纳米颗粒在体内表现出不同的行为，具体取决于其理化性质和给药途径。然而，聚乳酸-乙醇酸 (PLGA) 纳米颗粒的体内行为，尤其是经鼻给药时，仍未得到探索。此外，缺乏对不同行政途径之间吸收效率的比较分析。因此，在这里，我们的目标是全面研究 PLGA 纳米粒子在不同给药途径的实时体内行为。采用水包油单乳液法合成了三种尺寸的PLGA-NH2纳米粒子。我们使用荧光显微镜评估了小鼠巨噬细胞 RAW264.7 细胞对它们的摄取。为了实现实时跟踪，我们将 p-SCN-Bn-去铁胺与 PLGA-NH2 纳米粒子结合，并进一步用 89Zr-草酸盐对其进行放射性标记，然后通过不同途径给予小鼠。使用荧光激活细胞分选分析监测肺免疫细胞对纳米颗粒的内化。纳米颗粒尺寸为 294 ± 2.1（小）、522.5 ± 5.58（中）和 850 ± 18.52 nm（大）。荧光标记没有显着改变纳米颗粒的尺寸和电荷。 RAW264.7 细胞对小和大纳米颗粒的摄取水平相似，吞噬作用抑制主要减少大颗粒的内化。正电子发射断层扫描显示，鼻内给药导致肺部吸收最高且最具针对性，而静脉内给药导致主要在肝脏和脾脏中积累。相对于淋巴细胞，大纳米颗粒的鼻腔递送导致骨髓免疫细胞的摄取增强，而树突状细胞的摄取最初达到峰值，但随着时间的推移而下降。我们的研究为推进纳米医学和药物输送提供了宝贵的见解，并具有扩大纳米颗粒临床应用的潜力。