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新型结核纳米诊疗一体化制剂的研发与生物学评价。

Development and biological evaluation of a new nanotheranostic for tuberculosis.

机构信息

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro, Brazil.

Fiocruz Foundation, National Institute of Infectology, Rio de Janeiro, Brazil.

出版信息

Drug Deliv Transl Res. 2019 Feb;9(1):97-105. doi: 10.1007/s13346-018-0577-6.

Abstract

In this study, we developed, characterized, and tested in vivo polymeric nanoparticle of ethambutol labeled with 99mTc as nanoradiopharmaceutical for early diagnosis of tuberculosis by single-photon emission computed tomography, also as a therapeutic choice. Nanoparticles were developed by double emulsification. All characterization tests were performed, as scanning electron microscopy and dynamic light scattering. The labeling process with 99mTc was performed using the direct labeling process. In vitro and in vivo assays were performed with animals and cells. The results showed that a spherical ethambutol nanoparticle with a size range of 280-300 nm was obtained. The stability test showed that the nanoparticles were well labeled with 99mTc (> 99.1%) and keep labeled over 24 h. The biodistribution assay showed that almost 18% of the nanoparticles were uptake by the lung in infected mice (male C57Bl/6) with Mycobacterium bovis BCG (4 × 10 CFU/cavity), corroborating its use as a nanodrug for tuberculosis imaging. The results for the cell assay corroborate its therapeutical effect. We developed and efficiently tested a new nanodrug that can be used for both imaging and therapy of tuberculosis, acting as a novel nanotheranostic.

摘要

在这项研究中,我们开发、表征并测试了一种标记有 99mTc 的乙胺丁醇聚合物纳米粒子作为单光子发射计算机断层扫描(SPECT)早期诊断结核病的纳米放射性药物,同时也作为一种治疗选择。纳米粒子是通过双重乳化法开发的。所有的特性测试,如扫描电子显微镜和动态光散射都进行了。99mTc 的标记过程是通过直接标记过程进行的。在动物和细胞上进行了体外和体内实验。结果表明,得到了一种具有 280-300nm 粒径范围的球形乙胺丁醇纳米粒子。稳定性测试表明,纳米粒子与 99mTc 的标记非常好(>99.1%),并且在 24 小时内保持标记。生物分布实验表明,在感染了牛分枝杆菌 BCG(4×10 CFU/腔)的雄性 C57Bl/6 小鼠的肺部中,几乎有 18%的纳米粒子被摄取,这证实了它作为一种结核病成像的纳米药物的用途。细胞实验的结果证实了其治疗效果。我们开发并有效地测试了一种新的纳米药物,它可用于结核病的成像和治疗,作为一种新型的纳米治疗诊断学。

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