掺杂苯并咪唑的锌基金属有机框架对克鲁兹锥虫急性实验感染的疗效。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Drug Delivery and Translational Research Pub Date : 2025-04-01 Epub Date: 2024-07-07 DOI:10.1007/s13346-024-01664-0
Anahí Sosa-Arroniz, Aracely López-Monteon, Rodolfo Peña-Rodríguez, José María Rivera-Villanueva, Jesus Torres-Montero, Angel Ramos-Ligonio
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引用次数: 0

摘要

已有研究表明,金属有机框架(MOFs)可促进封装化合物穿过细胞膜,从而实现可控和选择性释放,从而提高封装化合物的活性。本研究调查了 BNZ@Zn-MOFs 对小鼠模型中的克鲁斯锥虫急性感染期的疗效。研究采用电洗脱法(EL)合成了 BNZ@Zn-MOFs,并通过机械化学方法掺杂了 BZN,然后使用扫描电子显微镜(SEM)、红外光谱(FTIR)和 X 射线衍射(XRD)对其进行了表征。BNZ@Zn-MOFs 在 3 小时内释放了 80% 的封装 BZN,在 NIH-3T3 和 HeLa 细胞中没有细胞毒性。此外,在 BALB/c 小鼠的急性实验性 T. cruzi 感染模型中,与游离 BZN 相比,该递送系统在 BZN 浓度明显较低的情况下就表现出了抗寄生虫活性。对处理过的小鼠进行的 PCR 分析表明,它们的组织中没有寄生虫 DNA,苏木精-伊红染色显示组织结构没有明显损伤。此外,血清中的肝功能酶水平保持不变,表明对肝功能没有不良影响。这种利用次优 BZN 剂量的给药系统既能保持药物活性,又能大大减少与南美锥虫病治疗相关的副作用。
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Efficacy of a Zn-based metalorganic framework doped with benznidazole on acute experimental Trypanosoma cruzi infection.

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.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
期刊最新文献
Correction: Immunomodulatory potential of rapamycin-loaded mesoporous silica nanoparticles: pore size-dependent drug loading, release, and in vitro cellular responses. Retraction Note: Ameliorative effect of rubiadin-loaded nanocarriers in STZ-NA-induced diabetic nephropathy in rats: formulation optimization, molecular docking, and in vivo biological evaluation. Correction: Long-acting parenteral formulations of hydrophilic drugs, proteins, and peptide therapeutics: mechanisms, challenges, and therapeutic benefits with a focus on technologies. Chitosan/carbomer nanoparticles- laden in situ gel for improved ocular delivery of timolol: in vitro, in vivo, and ex vivo study. Efficacy of a Zn-based metalorganic framework doped with benznidazole on acute experimental Trypanosoma cruzi infection.
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