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多孔硅纳米粒子药物载体系对溃疡性结肠炎的影响。

Effect of Porous Silicon Nanoparticle Drug-Loading System on Ulcerative Colitis.

机构信息

Department of Gastroenterology, Shandong University Qilu Hospital, Jinan City, 250012, Shandong Province, China.

Department of Health Care 1, Navy 971 Hospital, Qingdao City, 266071, Shandong Province, China.

出版信息

J Nanosci Nanotechnol. 2021 Feb 1;21(2):1118-1126. doi: 10.1166/jnn.2021.18699.

DOI:10.1166/jnn.2021.18699
PMID:33183451
Abstract

Ulcerative colitis (UC) is a non-specific intestinal inflammatory disease. UC occurred in developed countries in the past, but in the past 20 years, the incidence of UC in developing countries has also shown a clear upward trend. The hospitalization rate and surgical rate of UC have been high, and may lead to the occurrence of intestinal malignant tumors, which has greatly affected the quality of life and life expectancy of patients. Because of this, how to effectively treat UC has become a hotspot in modern gastrointestinal diseases. Due to the limitation of the dosage form of the drug and the special environment of the gastrointestinal tract, traditional oral drugs have the disadvantage of not being able to make the drug effective in specific lesions when treating inflammatory bowel disease. Therefore, it is of great scientific significance and application value to develop drug carriers that can target the inflammatory sites and slow-release drugs to treat inflammation. In this study, TNBS method was used to prepare a rat model of ulcerative colitis, and the effect of modified porous silicon nanoparticles as a drug carrier in the treatment of UC was investigated. We first induced acute enteritis model in C57BL/6 rats through TNBS, and then used in vivo fluorescence imaging and immunofluorescence staining technology to prove that porous silicon nanoparticles can indeed be specifically concentrated in the damaged part of the mouse intestine, and then administered by gastric administration. The drug method allows rats to take different types and concentrations of drug-loaded porous silicon nanoparticles, and finally collect relevant samples for evaluation of drug efficacy after the end of the administration cycle. The disease activity index showed the best gastrointestinal recovery in mice treated with modified drug-loaded porous silicon nanoparticles. The pathological analysis of rat colons using HE staining proved that the improved drug-loaded porous silicon nanoparticles had a more significant therapeutic effect. TUNEL staining results showed that the level of apoptosis in the colon injury site of rats treated with modified drug-loaded porous silicon nanoparticles was reduced. The test results of drug concentration in rat colon tissue blood also proved that porous silicon nanoparticle drug-loading system can reduce the release of inflammatory factors in vivo. Based on the TNBS-induced UC rat model, this paper evaluates the therapeutic effect of modified drug-loaded porous silicon nanoparticles. The results show that in the treatment of ulcerative colitis, the nanoparticle drug-loaded system is a more effective treatment way.

摘要

溃疡性结肠炎(UC)是一种非特异性肠道炎症性疾病。UC 过去在发达国家发生,但在过去 20 年中,发展中国家 UC 的发病率也呈现出明显的上升趋势。UC 的住院率和手术率均较高,可能导致肠道恶性肿瘤的发生,极大地影响了患者的生活质量和预期寿命。正因为如此,如何有效地治疗 UC 已成为现代胃肠病学的热点。由于药物剂型的限制和胃肠道的特殊环境,传统的口服药物在治疗炎症性肠病时存在不能使药物在特定病变部位发挥作用的缺点。因此,开发能够靶向炎症部位并缓释药物以治疗炎症的药物载体具有重要的科学意义和应用价值。本研究采用 TNBS 法制备大鼠溃疡性结肠炎模型,考察了改性多孔硅纳米粒子作为药物载体治疗 UC 的效果。我们首先通过 TNBS 诱导 C57BL/6 大鼠急性肠炎模型,然后通过体内荧光成像和免疫荧光染色技术证明多孔硅纳米粒子确实可以特异性地聚集在小鼠肠道受损部位,然后通过灌胃给药。该药物方法允许大鼠服用不同类型和浓度的载药多孔硅纳米粒子,最后在给药周期结束后收集相关样本进行药效评估。疾病活动指数显示,经改良载药多孔硅纳米粒子治疗的小鼠胃肠道恢复最好。HE 染色对大鼠结肠的病理分析证明,改良载药多孔硅纳米粒子具有更显著的治疗效果。TUNEL 染色结果显示,经改良载药多孔硅纳米粒子治疗的大鼠结肠损伤部位细胞凋亡水平降低。大鼠结肠组织血液中药物浓度的检测结果也证明,多孔硅纳米粒子载药系统可以减少体内炎症因子的释放。基于 TNBS 诱导的 UC 大鼠模型,本文评价了改良载药多孔硅纳米粒子的治疗效果。结果表明,在治疗溃疡性结肠炎方面,纳米粒子载药系统是一种更有效的治疗方法。

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