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用于治疗2型糖尿病的载二甲双胍聚合物基微泡/纳米颗粒

Metformin-Loaded Polymer-Based Microbubbles/Nanoparticles Generated for the Treatment of Type 2 Diabetes Mellitus.

作者信息

Cesur Sumeyye, Cam Muhammet Emin, Sayın Fatih Serdar, Su Sena, Harker Anthony, Edirisinghe Mohan, Gunduz Oguzhan

机构信息

Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.

London Centre for Nanotechnology and Department of Physics & Astronomy, University College London, London WC1E 6BT, U.K.

出版信息

Langmuir. 2022 May 3;38(17):5040-5051. doi: 10.1021/acs.langmuir.1c00587. Epub 2021 Jun 6.

DOI:10.1021/acs.langmuir.1c00587
PMID:34096296
Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is increasingly common all over the world with a high risk of progressive hyperglycemia and high microvascular and macrovascular complications. The currently used drugs in the treatment of T2DM have insufficient glucose control and can carry detrimental side effects. Several drug delivery systems have been investigated to decrease the side effects and frequency of dosage, and also to increase the effect of oral antidiabetic drugs. In recent years, the use of microbubbles in biomedical applications has greatly increased, and research into microactive carrier bubbles continues to generate more and more clinical interest. In this study, various monodisperse polymer nanoparticles at different concentrations were produced by bursting microbubbles generated using a T-junction microfluidic device. Morphological analysis by scanning electron microscopy, molecular interactions between the components by FTIR, drug release by UV spectroscopy, and physical analysis such as surface tension and viscosity measurement were carried out for the particles generated and solutions used. The microbubbles and nanoparticles had a smooth outer surface. When the microbubbles/nanoparticles were compared, it was observed that they were optimized with 0.3 wt % poly(vinyl alcohol) (PVA) solution, 40 kPa pressure, and a 110 μL/min flow rate, thus the diameters of the bubbles and particles were 100 ± 10 μm and 70 ± 5 nm, respectively. Metformin was successfully loaded into the nanoparticles in these optimized concentrations and characteristics, and no drug crystals and clusters were seen on the surface. Metformin was released in a controlled manner at pH 1.2 for 60 min and at pH 7.4 for 240 min. The process and structures generated offer great potential for the treatment of T2DM.

摘要

2型糖尿病(T2DM)是一种慢性代谢性疾病,在全球范围内日益普遍,具有进行性高血糖以及微血管和大血管并发症的高风险。目前用于治疗T2DM的药物对血糖的控制不足,并且可能产生有害的副作用。人们已经研究了几种药物递送系统,以减少副作用和给药频率,同时提高口服抗糖尿病药物的疗效。近年来,微泡在生物医学应用中的使用大幅增加,对微活性载体气泡的研究也继续引发越来越多的临床关注。在本研究中,通过使用T型结微流控装置产生的微泡破裂制备了不同浓度的各种单分散聚合物纳米颗粒。对所生成的颗粒和所用溶液进行了扫描电子显微镜形态分析、傅里叶变换红外光谱法分析成分之间的分子相互作用、紫外光谱法分析药物释放以及表面张力和粘度测量等物理分析。微泡和纳米颗粒具有光滑的外表面。当比较微泡/纳米颗粒时,发现它们在0.3 wt%聚乙烯醇(PVA)溶液、40 kPa压力和110 μL/min流速下得到了优化,因此气泡和颗粒的直径分别为100±10μm和70±5nm。二甲双胍成功以这些优化的浓度和特性负载到纳米颗粒中,并且在表面未观察到药物晶体和聚集体。二甲双胍在pH 1.2时60分钟内以及在pH 7.4时240分钟内以可控方式释放。所产生的过程和结构为T2DM的治疗提供了巨大潜力。

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