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具有生物相容性和生物降解性的铜原儿茶酸金属有机骨架作为利福平载体。

Biocompatible and biodegradable copper-protocatechuic metal-organic frameworks as rifampicin carrier.

机构信息

Center for Sustainable Resource Science, RIKEN, Yokohama, Japan; Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106-07, Taiwan.

Chemical Engineering Department, National Taiwan University of Science and Technology, Taipei 10607, Taiwan.

出版信息

Biomater Adv. 2023 Mar;146:213269. doi: 10.1016/j.bioadv.2022.213269. Epub 2022 Dec 22.

Abstract

Tuberculosis (TB) is a disease caused by the M. tuberculosis bacteria infection and is listed as one of the deadliest diseases to date. Despite the development of antituberculosis drugs, the need for long-term drug consumption and low patient commitment are obstacles to the success of TB treatment. A continuous drug delivery system that has a long-term effect is needed to reduce routine drug consumption intervals, suppress infection, and prevent the emergence of drug-resistant strains of M. tuberculosis. For this reason, biomolecule metal-organic framework (BioMOF) with good biocompatibility, nontoxicity, bioactivity, and high stability are becoming potential drug carriers. This study used a bioactive protocatechuic acid (PCA) as organic linker to prepare copper-based BioMOF Cu-PCA under base-modulated conditions. Detailed crystal analysis by the powder X-ray diffraction demonstrated that the Cu-PCA, with a chemical formula of CHOCu, crystalizes as triclinic in space group P1. Comprehensive physicochemical characterizations were provided using FTIR, SEM, XPS, TGA, EA, and N sorption. As a drug carrier, Cu-PCA showed a high maximum rifampicin (RIF) drug loading of 443.01 mg/g. Upon resuspension in PBS, the RIF and linkers release profile exhibited two-stage release kinetic profiles, which are well described by the Biphasic Dose Response (BiDoseResp) model. A complete release of these compounds (RIF and PCA) was achieved after ~9 h of mixing in PBS. Cu-PCA and RIF@Cu-PCA possessed antibacterial activity against Escherichia coli, and good biocompatibility is evidenced by the high viability of MH-S mice alveolar macrophage cells upon supplementations.

摘要

结核病(TB)是由结核分枝杆菌感染引起的疾病,被列为迄今为止最致命的疾病之一。尽管开发了抗结核药物,但长期药物消耗和低患者承诺仍是结核病治疗成功的障碍。需要一种具有长期效果的持续药物输送系统,以减少常规药物消耗间隔,抑制感染,并防止结核分枝杆菌耐药菌株的出现。出于这个原因,具有良好的生物相容性、低毒性、生物活性和高稳定性的生物分子金属有机骨架(BioMOF)正成为潜在的药物载体。本研究使用生物活性原儿茶酸(PCA)作为有机连接体,在碱调节条件下制备了基于铜的 BioMOF Cu-PCA。粉末 X 射线衍射的详细晶体分析表明,Cu-PCA 具有化学式为 CHOCu,在空间群 P1 中结晶为三斜晶系。通过 FTIR、SEM、XPS、TGA、EA 和 N 吸附对其进行了全面的物理化学特性分析。作为药物载体,Cu-PCA 表现出高达 443.01 mg/g 的最大利福平(RIF)药物负载量。在重新悬浮于 PBS 中时,RIF 和连接体的释放曲线表现出两阶段释放动力学曲线,这可以通过双相剂量反应(BiDoseResp)模型很好地描述。在 PBS 中混合约 9 小时后,这些化合物(RIF 和 PCA)完全释放。Cu-PCA 和 RIF@Cu-PCA 对大肠杆菌具有抗菌活性,并且 MH-S 小鼠肺泡巨噬细胞细胞补充后的高存活率证明了其良好的生物相容性。

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