Biocompatible porous metal-organic framework nanoparticles based on Fe or Zr for gentamicin vectorization
Biocompatible porous metal-organic framework nanoparticles based on Fe or Zr for gentamicin vectorization
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DOI：
10.1016/j.ejpb.2018.08.013
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发表时间：
2018-11-01
影响因子：
4.9
通讯作者：
Blanco-Prieto, M. J.
中科院分区：
文献类型：
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作者：
Unamuno, X.;Imbuluzqueta, E.;Blanco-Prieto, M. J.
由于其高孔隙率和多功能的组成和结构，纳米级金属有机框架（nanoMOF）最近被提议作为新型药物递送系统，并已被证明具有控制释放不同活性成分的重要能力和潜力。庆大霉素（GM；一种用于细菌性败血症治疗的广谱氨基糖苷类抗生素）具有巨大的治疗意义，但伴随高剂量和重复给药这种游离药物所带来的相关生物利用度和毒性缺点，使得有必要将其封装在新的纳米载体中。通过简单的浸渍方法将转基因物质封装在两种不同的多孔生物友好的铁和锆羧酸盐纳米MOF中，并使用大量技术（X射线粉末衍射-XRPD、傅里叶变换红外光谱-FTIR、热重分析-TGA、N-2吸附、扫描电子显微镜-SEM、动态光散射-DLS、zeta电位、荧光光谱和分子模拟）对所得含转基因固体进行全面表征。使用生物相容性介孔苯均三酸铁(III)纳米颗粒(NP) MIL-100(Fe)（MIL：来自拉瓦锡研究所的材料）获得了高可重复的包封率，达到每毫克制剂600μg GM。还使用不同的口服和静脉注射模拟生理条件进行了体外 GM 递送研究，当使用无蛋白培养基时，抗生素在 8 小时内完全释放，但在存在蛋白的情况下释放率较低。此外，在两种不同的细胞系上研究了含有 GM 的 MIL-100(Fe) NP 的体外毒性：白血病单核细胞 (THP-1) 和贴壁成纤维细胞 (NIH/3T3)。这些nanoMOF具有低细胞毒性，IC50值高达1 mg.mL(-1)，确保24小时后细胞充分增殖。最后，分别对两种革兰氏阳性菌和一种革兰氏阴性菌：金黄色葡萄球菌、表皮葡萄球菌和铜绿假单胞菌进行抗菌活性研究。负载GM的MIL-100(Fe) NP表现出与游离GM相同的活性，证实释放的GM的抗生素活性是保守的。
Due to their high porosity and versatile composition and structure, nanoscaled Metal-Organic Frameworks (nanoMOFs) have been recently proposed as novel drug delivery systems, and have been demonstrated to have important capacities and potential for controlled release of different active ingredients. Gentamicin (GM; a broad spectrum aminoglycoside antibiotic indicated in bacterial septicemia therapy) has great therapeutic interest, but the associated bioavailability and toxicity drawbacks accompanying high doses and repeated administration of this free drug make its encapsulation inside new nanocarriers necessary. GM encapsulation within two different porous biofriendly Fe and Zr-carboxylates nanoMOFs was performed by a simple impregnation method, with full characterization of the resulting GM-containing solid using a large panel of techniques (X ray powder diffraction-XRPD, Fourier transform infrared spectroscopy-FTIR, thermogravimetric analysis-TGA, N-2 sorption, scanning electron microscopy-SEM, dynamic light scattering-DLS, zeta-potential, fluorescence spectroscopy and molecular simulations). High reproducible encapsulation rates, reaching 600 mu g of GM per mg of formulation, were obtained using the biocompatible mesoporous iron(III) trimesate nanoparticles (NPs) MIL-100(Fe) (MIL: Materials from Institut Lavoisier). In vitro GM delivery studies were also carried out using different oral and intravenous simulated physiological conditions, with complete antibiotic release within 8 h when using protein free media, but lower release rates in the presence of proteins. Furthermore, in vitro toxicity of GM-containing MIL-100(Fe) NPs was investigated on two different cell lines: a monocyte from leukemia (THP-1) and adherent fibroblastoid cells (NIH/3T3). These nanoMOFs had a low cytotoxic profile with IC50 values up to 1 mg.mL(-1), ensuring adequate cell proliferation after 24 h. Finally, antibacterial activity studies were carried out on two Gram-positive bacteria and one Gram-negative bacterium: S. aureus, S. epidermidis and P. aeruginosa, respectively. GM-loaded MIL-100(Fe) NPs exhibited the same activity as free GM, confirming that the antibiotic activity of the released GM was conserved.