介孔二氧化硅给药作为华法林毒性管理的新策略:一项体外和体内研究。

IF 3.1 Q2 PHARMACOLOGY & PHARMACY
Advanced pharmaceutical bulletin Pub Date : 2024-12-30 Epub Date: 2024-10-02 DOI:10.34172/apb.42665
Fatemeh Farjadian, Fatemeh Parsi, Reza Heidari, Khatereh Zarkesh, Hamid Reza Mohammadi, Soliman Mohammadi-Samani, Lobat Tayebi
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引用次数: 0

摘要

目的:华法林是应用最广泛的抗凝血剂之一,其作用是抑制维生素K环氧化物还原酶。华法林过量,无论是有意还是无意,都可能导致危及生命的出血。在这里,我们提出了一种基于介孔二氧化硅的新型华法林吸附剂,可以作为华法林毒性的解毒剂。方法:采用软模板法和去模板法制备氨基功能化介孔二氧化硅(MS-NH2)。利用傅里叶变换红外光谱(FT-IR)和x射线衍射(XRD)对制备的化合物的结构和官能团进行了研究。扫描电镜(SEM)和透射电镜(TEM)检查形貌。在pH=7.4和pH=1.2条件下,考察MS-NH2对华法林的体外吸附能力。在对照和华法林过量动物模型中进行体内评价。给药过量动物灌胃MS-NH2。在动物血清中评估器官损伤的生物标志物。结果:MS-NH2相对均匀,呈球形,直径为400 nm,具有多孔结构。合成的颗粒具有较大的表面积(1015 m2 g-1),平均孔径为2.4 nm,对华法林的吸附量为1666 mg/g。体内研究显示,华法林中毒小鼠口服MS-NH2可引起显著差异(P2组与组织损伤相关的生物标志物,如胆红素、乳酸脱氢酶(LDH)、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)显著降低)。结论:MS-NH2给药可有效治疗华法林中毒,并有可能减轻华法林中毒的不良反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mesoporous Silica Administration as a New Strategy in the Management of Warfarin Toxicity: An In-Vitro and In-Vivo Study.

Purpose: Warfarin is one of the most widely used anticoagulants that functions by inhibiting vitamin K epoxide reductase. Warfarin overdose, whether intentional or unintentional, can cause life-threatening bleeding. Here, we present a novel warfarin adsorbent based on mesoporous silica that could serve as an antidote to warfarin toxicity.

Methods: Amino-functionalized mesoporous silica (MS-NH2) was synthesized based on the co-condensation method through a soft template technique followed by template removal. The prepared structure and functional group were studied by Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) checked the morphology. The capacity of MS-NH2 in the adsorption of warfarin was evaluated in vitro, at pH=7.4 and pH=1.2. In vivo evaluations were performed in control and warfarin-overdosed animal models. Overdosed animals were treated with MS-NH2 by oral gavage. Biomarkers of organ injury were assessed in animal serum.

Results: The MS-NH2 was relatively uniform, spherical with defined diameters (400 nm) and porous structure. Synthesized particles had a large surface area (1015 m2 g-1) and mean pore diameter of 2.4 nm which led to considerable adsorption capacity for warfarin 1666 mg/g. In vivo studies revealed that oral administration of MS-NH2 in mice poisoned with warfarin caused a significant difference (P<0.05) in the International Normalized Ratio (INR) and prothrombin time (PT). Moreover, the warfarin with MS-NH2 group demonstrated a notable decrease in biomarkers associated with tissue damage, such as bilirubin, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST).

Conclusion: The results confirm that MS-NH2 administration can be an effective treatment for warfarin toxicity and could potentially mitigate the adverse effects of warfarin poisoning.

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来源期刊
Advanced pharmaceutical bulletin
Advanced pharmaceutical bulletin PHARMACOLOGY & PHARMACY-
CiteScore
6.80
自引率
2.80%
发文量
51
审稿时长
12 weeks
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