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Liposome-siderophore conjugates loaded with moxifloxacin serve as a model for drug delivery against Mycobacterium tuberculosis
International Journal of Pharmaceutics ( IF 5.8 ) Pub Date : 2024-03-26 , DOI: 10.1016/j.ijpharm.2024.124050
Camila Maringolo Ribeiro , Cesar Augusto Roque-Borda , Maria Carolina Franzini , Karyn Fernanda Manieri , Fernanda Manaia Demarqui , Débora Leite Campos , Rachel Temperani Amaral Machado , Isabel Cristiane da Silva , Marcela Tavares Luiz , Leonardo Delello Di Filippo , Patrícia Bento da Silva , Márcia Cristina Oliveira da Rocha , Sônia Nair Báo , Domiziana Masci , Guilherme F.S. Fernandes , Daniele Castagnolo , Marlus Chorilli , Fernando Rogério Pavan

Tuberculosis (TB) is an infectious disease that annually affects millions of people, and resistance to available antibiotics has exacerbated this situation. Another notable characteristic of , the primary causative agent of TB, is its ability to survive inside macrophages, a key component of the immune system. In our quest for an effective and safe treatment that facilitates the targeted delivery of antibiotics to the site of infection, we have proposed a nanotechnology approach based on an iron chelator. Iron chelators are the primary mechanism by which bacteria acquire iron, a metal essential for their metabolism. Four liposomes were synthesized and characterized using the dynamic light scattering technique (DLS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). All of these methods revealed the presence of spherical particles, approximately 200 nm in size. NTA indicated a concentration of around 10 particles/mL. We also developed and validated a high-performance liquid chromatography method for quantifying Moxifloxacin to determine encapsulation efficiency (EE) and release profiles (RF). The EE was 51.31 % for LipMox and 45.76 % for LipIchMox. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the phagocytosis of liposomal vesicles by macrophages. Functionalizing liposomes with iron chelators can offer significant benefits for TB treatment, such as targeted drug delivery to intracellular bacilli through the phagocytosis of liposomal particles by cells like macrophages.

中文翻译:

负载莫西沙星的脂质体-铁载体缀合物作为抗结核分枝杆菌的药物递送模型

结核病 (TB) 是一种传染病,每年影响数百万人,而对现有抗生素的耐药性加剧了这种情况。结核病的主要病原体的另一个显着特征是它能够在巨噬细胞内生存,而巨噬细胞是免疫系统的关键组成部分。在我们寻求一种有效且安全的治疗方法,以促进抗生素有针对性地输送到感染部位的过程中,我们提出了一种基于铁螯合剂的纳米技术方法。铁螯合剂是细菌获取铁的主要机制,铁是细菌新陈代谢所必需的金属。使用动态光散射技术(DLS)、纳米颗粒跟踪分析(NTA)和透射电子显微镜(TEM)合成并表征了四种脂质体。所有这些方法都揭示了尺寸约为 200 nm 的球形颗粒的存在。 NTA 显示浓度约为 10 个颗粒/mL。我们还开发并验证了一种高性能液相色谱方法,用于定量莫西沙星,以确定包封效率 (EE) 和释放曲线 (RF)。 LipMox 的 EE 为 51.31%,LipIchMox 的 EE 为 45.76%。扫描电子显微镜(SEM)和透射电子显微镜(TEM)证实了巨噬细胞对脂质体囊泡的吞噬作用。用铁螯合剂功能化脂质体可以为结核病治疗带来显着益处,例如通过巨噬细胞等细胞吞噬脂质体颗粒将靶向药物递送至细胞内杆菌。
更新日期:2024-03-26
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