Impact of administration route on nanocarrier biodistribution in a murine colitis model.

IF 2.6 4区 材料科学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Journal of Experimental Nanoscience Pub Date : 2022-01-01 Epub Date: 2022-10-19 DOI:10.1080/17458080.2022.2134563
Catherine C Applegate, Hongping Deng, Brittany L Kleszynski, Tzu-Wen L Cross, Christian J Konopka, L Wawrzyniec Dobrucki, Erik R Nelson, Matthew A Wallig, Andrew M Smith, Kelly S Swanson
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引用次数: 0

Abstract

The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Although current diagnostic and disease monitoring tests for IBD sensitively detect gut inflammation, they lack the molecular and cellular specificity of positron emission tomography (PET). In this proof-of-concept study, we use a radiolabeled macrophage-targeted nanocarrier probe (64Cu-NOTA-D500) administered by oral, enema, and intraperitoneal routes to evaluate the delivery route dependence of biodistribution across healthy and diseased tissues in a murine model of dextran sodium sulfate (DSS)-induced colitis. High inter-subject variability of probe uptake in intestinal tissue was reduced by normalization to uptake in liver or total intestines. Differences in normalized uptake between healthy and DSS colitis animal intestines were highest for oral and IP routes. Differences in absolute liver uptake reflected a possible secondary diagnostic metric of IBD pathology. These results should inform the preclinical development of inflammation-targeted contrast agents for IBD and related gut disorders to improve diagnostic accuracy.

给药途径对小鼠结肠炎模型中纳米载体生物分布的影响。
炎症性肠病(IBD)的发病率在全球范围内呈上升趋势。尽管目前IBD的诊断和疾病监测测试能够灵敏地检测肠道炎症,但它们缺乏正电子发射断层扫描(PET)的分子和细胞特异性。在这项概念验证研究中,我们使用放射性标记的巨噬细胞靶向纳米载体探针(64Cu-NOTA-D500),通过口服、灌肠和腹膜内途径给药,以评估右旋糖酐硫酸钠(DSS)诱导的结肠炎小鼠模型中健康和患病组织中生物分布的递送途径依赖性。肠组织中探针摄取的高受试者间变异性通过正常化为肝脏或整个肠道中的摄取而降低。健康和DSS结肠炎动物肠道之间的正常摄取差异在口服和IP途径中最高。绝对肝脏摄取的差异反映了IBD病理学的可能的次要诊断指标。这些结果应为炎症性肠病和相关肠道疾病的炎症靶向造影剂的临床前开发提供信息,以提高诊断准确性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Experimental Nanoscience
Journal of Experimental Nanoscience 工程技术-材料科学:综合
CiteScore
4.10
自引率
25.00%
发文量
39
审稿时长
6.5 months
期刊介绍: Journal of Experimental Nanoscience, an international and multidisciplinary journal, provides a showcase for advances in the experimental sciences underlying nanotechnology and nanomaterials. The journal exists to bring together the most significant papers making original contributions to nanoscience in a range of fields including biology and biochemistry, physics, chemistry, chemical, electrical and mechanical engineering, materials, pharmaceuticals and medicine. The aim is to provide a forum in which cross fertilization between application areas, methodologies, disciplines, as well as academic and industrial researchers can take place and new developments can be encouraged.
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