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掺杂苯硝唑的锌基金属有机框架对急性实验性克氏锥虫感染的疗效。

Efficacy of a Zn-based metalorganic framework doped with benznidazole on acute experimental Trypanosoma cruzi infection.

作者信息

Sosa-Arroniz Anahí, López-Monteon Aracely, Peña-Rodríguez Rodolfo, Rivera-Villanueva José María, Torres-Montero Jesus, Ramos-Ligonio Angel

机构信息

LADISER, Inmunología y Biología Molecular, Edificio D, Facultad de Ciencias Químicas, Universidad Veracruzana (UV), Prolongación de Oriente 6 #1009; Colonia Rafael Alvarado; C.P., Orizaba, 94340, Veracruz, México.

Maestría en Ciencias en Procesos Biológicos, Facultad de Ciencias Químicas, Universidad Veracruzana, Orizaba, 94340, Veracruz, México.

出版信息

Drug Deliv Transl Res. 2025 Apr;15(4):1221-1234. doi: 10.1007/s13346-024-01664-0. Epub 2024 Jul 7.

DOI:10.1007/s13346-024-01664-0
PMID:38972897
Abstract

Metal-Organic Frameworks (MOFs) have been shown to enhance the activity of encapsulated compounds by facilitating their passage across cell membranes, thereby enabling controlled and selective release. This study investigates the efficacy of BNZ@Zn-MOFs against the acute phase of Trypanosoma cruzi infection in a mouse model. The particles were synthesized by electroelution (EL), doped with BZN via mechanochemistry, and characterized using scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and X-ray diffraction (XRD). BNZ@Zn-MOFs released 80% of the encapsulated BZN within 3 h, demonstrating no cytotoxicity in NIH-3T3 and HeLa cells. Furthermore, in a model of acute experimental T. cruzi-infection in BALB/c mice, the delivery system exhibited antiparasitic activity at a significantly lower BZN concentration compared to free BZN treatment. PCR analysis of treated mice revealed no parasite DNA in their tissues, and hematoxylin-eosin staining showed no apparent damage to tissue architecture. Additionally, serum levels of liver function enzymes remained unchanged, indicating no adverse effects on liver function. This delivery system, utilizing suboptimal BZN doses, enables the preservation of drug activity while potentially facilitating a substantial decrease in side effects associated with Chagas disease treatment.

摘要

金属有机框架材料(MOFs)已被证明可通过促进包封化合物穿过细胞膜来增强其活性,从而实现可控的选择性释放。本研究在小鼠模型中研究了BNZ@Zn-MOFs对克氏锥虫感染急性期的疗效。通过电洗脱法(EL)合成颗粒,通过机械化学法掺杂BZN,并使用扫描电子显微镜(SEM)、红外光谱(FTIR)和X射线衍射(XRD)对其进行表征。BNZ@Zn-MOFs在3小时内释放了80%的包封BZN,在NIH-3T3和HeLa细胞中无细胞毒性。此外,在BALB/c小鼠急性实验性克氏锥虫感染模型中,与游离BZN治疗相比,该递送系统在显著更低的BZN浓度下表现出抗寄生虫活性。对治疗小鼠的PCR分析显示其组织中无寄生虫DNA,苏木精-伊红染色显示组织结构无明显损伤。此外,肝功能酶的血清水平保持不变,表明对肝功能无不良影响。这种利用次优剂量BZN的递送系统能够在保留药物活性的同时,可能有助于大幅降低与恰加斯病治疗相关的副作用。

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Use of Nanocarriers Containing Antitrypanosomal Drugs for the Treatment of Chagas Disease.使用含有抗锥虫药物的纳米载体治疗恰加斯病。
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Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies.
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Formulation of benznidazole-lipid nanocapsules: Drug release, permeability, biocompatibility, and stability studies.苯硝唑脂质纳米胶囊的制剂研究:药物释放、渗透性、生物相容性和稳定性研究。
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