Peng Cong, Luan Haopeng, Shang Qisong, Xiang Wei, Yasin Parhat, Song Xinghua
Department of Spine Surgery, The Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830002, China.
Bioconjug Chem. 2025 May 21;36(5):1021-1033. doi: 10.1021/acs.bioconjchem.5c00062. Epub 2025 Apr 22.
Tuberculosis, caused by , is the leading cause of mortality attributed to a single infectious agent. Following macrophage invasion, M. tuberculosis uses various mechanisms to evade immune responses and to resist antituberculosis drugs. This study aimed to develop a targeted drug delivery system utilizing mannosamine (MAN)-modified nanoparticles (NPs) composed of poly(lactic--glycolic acid)-polyethylene glycol (PLGA-PEG), loaded with rifapentine and isoniazid, to enhance macrophage-directed therapy and enhance bacterial elimination. PLGA-PEG copolymer was modified with mannosamine through an amidation reaction. Rifapentine- and isoniazid-loaded PLGA-PEG-MAN NPs were synthesized by using the double emulsion solvent evaporation technique. The NPs exhibited an average particle size of 117.67 nm and displayed favorable physicochemical properties without evidence of cellular or hemolytic toxicity. The drug loading rates were 11.73% for rifapentine and 5.85% for isoniazid. Sustained drug release was achieved over a period exceeding 72 h, with antibacterial activity remaining intact during encapsulation. Synergistic bactericidal effects were noted. Additionally, mannosamine-modified NPs enhanced the phagocytic activity of macrophages via mannose receptor-mediated endocytosis, thereby improving drug delivery efficiency and significantly boosting the antibacterial efficacy of the NPs within macrophages. Pathological staining and biochemical analysis of rat organs following intravenous injection indicated that the NPs did not cause any significant toxic side effects in vivo. The findings of this study indicate that mannosamine-modified PLGA-PEG NPs loaded with rifapentine and isoniazid represent a promising drug delivery system for targeting macrophages to enhance the efficacy of antitubercular therapy.
由结核分枝杆菌引起的结核病是单一感染源导致死亡的主要原因。巨噬细胞被侵袭后，结核分枝杆菌利用多种机制逃避免疫反应并抵抗抗结核药物。本研究旨在开发一种靶向给药系统，该系统利用由聚乳酸-乙醇酸-聚乙二醇（PLGA-PEG）组成、用甘露糖胺（MAN）修饰的纳米颗粒（NPs），负载利福喷汀和异烟肼，以增强针对巨噬细胞的治疗并促进细菌清除。通过酰胺化反应，用甘露糖胺对PLGA-PEG共聚物进行修饰。采用双乳液溶剂蒸发技术合成了负载利福喷汀和异烟肼的PLGA-PEG-MAN NPs。这些NPs的平均粒径为117.67 nm，具有良好的理化性质，且无细胞毒性或溶血毒性迹象。利福喷汀的载药率为11.73%，异烟肼的载药率为5.85%。在超过72小时的时间内实现了药物的持续释放，包封过程中抗菌活性保持不变。观察到协同杀菌作用。此外，甘露糖胺修饰的NPs通过甘露糖受体介导的内吞作用增强了巨噬细胞的吞噬活性，从而提高了给药效率，并显著提高了NPs在巨噬细胞内的抗菌效果。静脉注射后对大鼠器官进行的病理染色和生化分析表明，这些NPs在体内未引起任何明显的毒副作用。本研究结果表明，负载利福喷汀和异烟肼的甘露糖胺修饰的PLGA-PEG NPs是一种有前景的给药系统，可靶向巨噬细胞以提高抗结核治疗的疗效。
