Intranasal delivery of metformin using metal–organic framework (MOF)-74-Mg nanocarriers

IF 23.2 2区材料科学 Q1 MATERIALS SCIENCE, COMPOSITES

Advanced Composites and Hybrid Materials Pub Date : 2025-01-18 DOI:10.1007/s42114-025-01227-y

Muzhaozi Yuan, Zongsu Han, Yogish Somayaji, Nguyen Nguyen, Hanwen Hu, Leelavathi N. Madhu, Sahithi Attaluri, Maheedhar Kodali, Yihao Yang, Yu-Chuan Hsu, Avik Ahuja, Rahul Srinivasan, Jean-Philippe Pellois, Hong-Cai Zhou, Ashok K. Shetty, Ya Wang

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引用次数: 0

Abstract

Dosage tolerance is one of the translational challenges of using metformin (Met) in brain therapeutics. This paper presents metal–organic framework (MOF)-74-Mg nanocarriers (NCs) for intranasal (IN) delivery of brain-specific agents with a prolonged release time. We confirmed their excellent biocompatibility (5 mg/mL) and intrinsic fluorescence properties (370/500 nm excitation/emission peak) in Neuro-2A cells. This NC exhibited a high Met loading rate (10% wt/wt) and a sustained and prolonged release pattern of Met (90% release in 16 h) in Dulbecco’s Modified Eagle Medium. We observed an optimal brain accumulation of Met-MOF (9% of the injected dosage) 8 h after IN injection. This percentage is at least 82 times higher than oral administration. Confocal imaging demonstrated significantly higher uptake of Met-MOF, 45 min after IN injection, by 79–85% neurons and 93–97% microglia than astrocytes and oligodendrocytes across 5xFAD mouse brain regions, including hippocampus and striatum. These results suggest MOF-74-Mg is a potential NC for high brain Met accumulation, real-time imaging, and prolonged and sustained release of Met and other neurotherapeutic agents that are challenging to deliver using traditional carriers and administration routes.

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使用金属-有机框架(MOF)-74 mg纳米载体鼻内给药二甲双胍

剂量耐受性是二甲双胍（Met）在脑治疗中的转化挑战之一。本文提出了一种金属-有机框架(MOF)-74-Mg纳米载体（NCs），用于脑特异性药物的鼻内递送，具有较长的释放时间。我们证实了它们在神经- 2a细胞中具有良好的生物相容性（5 mg/mL）和固有的荧光特性（370/500 nm激发/发射峰）。该NC在Dulbecco 's Modified Eagle培养基中表现出高Met加载率（10% wt/wt）和持续和延长的Met释放模式（16小时内释放90%）。我们观察到，注射IN后8小时，Met-MOF（注射剂量的9%）在脑内蓄积最佳。这一比例至少是口服给药的82倍。共聚焦成像显示，注射IN后45分钟，在5xFAD小鼠的大脑区域，包括海马和纹状体，79-85%的神经元和93-97%的小胶质细胞对Met-MOF的摄取明显高于星形胶质细胞和少突胶质细胞。这些结果表明MOF-74-Mg是一种潜在的NC，可用于高脑Met积累，实时成像，延长和持续释放Met和其他神经治疗药物，这些药物具有传统载体和给药途径的挑战性。

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来源期刊

Advanced Composites and Hybrid Materials Multiple-

CiteScore

26.00

自引率

21.40%

发文量

185

期刊介绍： Advanced Composites and Hybrid Materials is a leading international journal that promotes interdisciplinary collaboration among materials scientists, engineers, chemists, biologists, and physicists working on composites, including nanocomposites. Our aim is to facilitate rapid scientific communication in this field. The journal publishes high-quality research on various aspects of composite materials, including materials design, surface and interface science/engineering, manufacturing, structure control, property design, device fabrication, and other applications. We also welcome simulation and modeling studies that are relevant to composites. Additionally, papers focusing on the relationship between fillers and the matrix are of particular interest. Our scope includes polymer, metal, and ceramic matrices, with a special emphasis on reviews and meta-analyses related to materials selection. We cover a wide range of topics, including transport properties, strategies for controlling interfaces and composition distribution, bottom-up assembly of nanocomposites, highly porous and high-density composites, electronic structure design, materials synergisms, and thermoelectric materials. Advanced Composites and Hybrid Materials follows a rigorous single-blind peer-review process to ensure the quality and integrity of the published work.