Boltnarova Barbora, Durinova Anna, Jandova Lenka, Micuda Stanislav, Kucera Otto, Pavkova Ivona, Machacek Miloslav, Nemeckova Ivana, Vojta Marek, Dusek Jan, Krutakova Maria, Nachtigal Petr, Pavek Petr, Holas Ondrej
Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, Hradec Kralove, 50005, Czech Republic.
Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, Hradec Kralove, 50005, Czech Republic.
Macromol Biosci. 2025 Feb;25(2):e2400411. doi: 10.1002/mabi.202400411. Epub 2024 Nov 29.
Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.
糖皮质激素是强效抗炎药物，尽管其使用会伴有严重的副作用。将糖皮质激素载入合适的纳米载体可显著降低这些不良影响。巨噬细胞在炎症中起关键作用，使其成为载有糖皮质激素的纳米载体的重要作用靶点。本研究的主要目的是开发一种专门靶向肝脏巨噬细胞的载有糖皮质激素的聚乳酸-羟基乙酸共聚物（PLGA）纳米载体，从而使糖皮质激素能在炎症部位局部释放。采用纳米沉淀法合成了用于被动靶向巨噬细胞的载有醋酸地塞米松（DA）的PLGA纳米球。制备了两种粒径范围为100 - 300 nm的PLGA纳米球，DA载入效率达到19%。结果表明纳米球可在3天内持续释放DA。使用小鼠骨髓来源的巨噬细胞进行的流式细胞术分析表明，荧光染料标记的PLGA纳米球能有效内化，尤其是进入促炎性巨噬细胞。在用载有DA的PLGA纳米球处理后，观察到促炎性细胞因子基因mRNA显著下调，且无明显细胞毒性。随后在小鼠体内进行的实验通过体内成像、流式细胞术和荧光显微镜证实了静脉给药后纳米球在肝脏巨噬细胞中的特异性蓄积。综上所述，数据表明载有DA的PLGA纳米球是一种有前景的用于治疗炎症性肝病的药物递送系统。
