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可吸入喷雾干燥万古霉素涂层磁性纳米颗粒用于肺部局部递药。

Respirable spray dried vancomycin coated magnetic nanoparticles for localized lung delivery.

机构信息

Department of Bioengineering, The University of Kansas, Lawrence, KS 66045, USA.

Smyth Lab, College of Pharmacy, University of Texas at Austin, TX 78712, USA.

出版信息

Int J Pharm. 2022 Jan 5;611:121318. doi: 10.1016/j.ijpharm.2021.121318. Epub 2021 Nov 24.

Abstract

Bacterial pneumonia is a common pulmonary infection responsible for premature death. Biomaterials based-carriers loaded with antibiotics enhance drug potency through localizing the therapy, minimizing the associated adverse effects, and improving patient compliance. Herein, this study reports the preparation of an inhalable dry powder formulation composed of a nano-in-microparticles. Vancomycin was adsorbed on the core of magnetic nanoparticles followed by spray drying into lactose/dextran to optimize the aerodynamic performance and allow the local delivery of the drug into the bacterial pneumonia infection site. Lactose and Dextran are polysaccharides commonly used for pulmonary delivery due to their optimum aerodynamic performance and biocompatibility. The preparation of the nano-in-micro particles with optimum properties was confirmed using FTIR, TEM, SEM, Laser-diffraction, ICP-AES and TGA. The TEM micrographs confirmed the formation of spherical magnetic nanoparticles with a diameter 14.7 ± 5.9 nm and a coating thickness 3 - 16 nm, while laser diffraction showed that outer microparticles exhibited a mean diameter < 5 µm. The formulations demonstrated a promising activity against S. aureus and MRSA and better biocompatibility using MTT assay. In vivo safety and pharmacokinetic studies confirmed the localization of VAN in lung tissue and minimized adverse effects compared to free VAN. Therefore, the developed nano-in-microparticles confers a good potential for eradication of lung infections.

摘要

细菌性肺炎是一种常见的肺部感染,可导致过早死亡。基于生物材料的载体负载抗生素通过定位治疗、最小化相关不良反应和提高患者依从性来增强药物效力。在此,本研究报告了一种可吸入干粉制剂的制备,该制剂由纳米颗粒载入微颗粒组成。万古霉素被吸附在磁性纳米颗粒的核心上,然后通过喷雾干燥到乳糖/葡聚糖中,以优化空气动力学性能并允许药物局部递送到细菌性肺炎感染部位。乳糖和葡聚糖由于其最佳的空气动力学性能和生物相容性,是常用于肺部给药的多糖。使用 FTIR、TEM、SEM、激光衍射、ICP-AES 和 TGA 确认了具有最佳性能的纳米颗粒载入微颗粒的制备。TEM 显微照片证实了直径为 14.7 ± 5.9nm 且涂层厚度为 3-16nm 的球形磁性纳米颗粒的形成,而激光衍射表明外层微颗粒的平均直径 < 5µm。该制剂在体外对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌表现出有前途的活性,并且通过 MTT 测定法显示出更好的生物相容性。体内安全性和药代动力学研究证实,与游离万古霉素相比,VAN 在肺部组织中的定位和不良反应最小化。因此,开发的纳米颗粒载入微颗粒具有消除肺部感染的良好潜力。

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