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探索利福平与抗坏血酸负载海藻酸钠纳米颗粒的细胞毒性、肺部分布和细胞摄取及其作为肺部细胞内感染治疗的应用。

Exploring the Toxicity, Lung Distribution, and Cellular Uptake of Rifampicin and Ascorbic Acid-Loaded Alginate Nanoparticles as Therapeutic Treatment of Lung Intracellular Infections.

机构信息

UNITEFA, CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina.

Instituto de Investigación Médica Mercedes y Martín Ferreyra, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba (INIMEC-CONICET-UNC), Córdoba X5000HUA, Argentina.

出版信息

Mol Pharm. 2021 Mar 1;18(3):807-821. doi: 10.1021/acs.molpharmaceut.0c00692. Epub 2020 Dec 24.

Abstract

Nanotechnology is a very promising technological tool to combat health problems associated with the loss of effectiveness of currently used antibiotics. Previously, we developed a formulation consisting of a chitosan and tween 80-decorated alginate nanocarrier that encapsulates rifampicin and the antioxidant ascorbic acid (RIF/ASC), intended for the treatment of respiratory intracellular infections. Here, we investigated the effects of RIF/ASC-loaded NPs on the respiratory mucus and the pulmonary surfactant. In addition, we evaluated their cytotoxicity for lung cells , and their biodistribution on rat lungs after their intratracheal administration. Findings herein demonstrated that RIF/ASC-loaded NPs display a favorable lung biocompatibility profile and a uniform distribution throughout lung lobules. RIF/ASC-loaded NPs were mainly uptaken by lung macrophages, their primary target. In summary, findings show that our novel designed RIF/ASC NPs could be a suitable system for antibiotic lung administration with promising perspectives for the treatment of pulmonary intracellular infections.

摘要

纳米技术是一种非常有前途的技术工具,可以用来解决与目前使用的抗生素效果降低相关的健康问题。此前,我们开发了一种由壳聚糖和聚山梨酯 80 修饰的海藻酸钠纳米载体组成的制剂,该制剂包封了利福平(RIF)和抗氧化剂抗坏血酸(ASC),用于治疗呼吸道细胞内感染。在这里,我们研究了载 RIF/ASC 的 NPs 对呼吸道粘液和肺表面活性剂的影响。此外,我们评估了它们对肺细胞的细胞毒性,以及它们经气管内给药后在大鼠肺部的生物分布。研究结果表明,载 RIF/ASC 的 NPs 具有良好的肺生物相容性和在整个肺小叶中的均匀分布。载 RIF/ASC 的 NPs 主要被肺巨噬细胞摄取,肺巨噬细胞是它们的主要靶细胞。总之,研究结果表明,我们设计的新型 RIF/ASC NPs 可能是一种适合肺部抗生素给药的系统,为治疗肺部细胞内感染提供了有前景的治疗方法。

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