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利用个体化梯度筛选射流层流技术进行胰腺β细胞递送的新型生物技术微囊化方法:胆汁酸支持细胞能量生成机制。

New Biotechnological Microencapsulating Methodology Utilizing Individualized Gradient-Screened Jet Laminar Flow Techniques for Pancreatic β-Cell Delivery: Bile Acids Support Cell Energy-Generating Mechanisms.

作者信息

Mooranian Armin, Negrulj Rebecca, Takechi Ryu, Jamieson Emma, Morahan Grant, Al-Salami Hani

机构信息

Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University , Perth, Western Australia 6102, Australia.

School of Public Health, Curtin Health Innovation Research Institute, Curtin University , Perth, Western Australia 6102, Australia.

出版信息

Mol Pharm. 2017 Aug 7;14(8):2711-2718. doi: 10.1021/acs.molpharmaceut.7b00220. Epub 2017 Jul 17.

Abstract

In previous studies, we developed a new technique (ionic gelation vibrational jet flow; IGVJF) in order to encapsulate pancreatic β-cells, for insulin in vivo delivery, and diabetes treatment. The fabricated microcapsules showed good morphology but limited cell functions. Thus, this study aimed to optimize the IGVJF technique, by utilizing integrated electrode tension, coupled with high internal vibration, jet-flow polymer stream rate, ionic bath-gelation concentrations, and gelation time stay. The study also utilized double inner/outer nozzle segmented-ingredient flow of microencapsulating dispersion, in order to form β-cell microcapsules. Furthermore, a microcapsule-stabilizing bile acid was added, and microcapsule's stability and cell functions measured. Buchi-based built-in system utilizing IGVJF technology was screened to produce best microcapsule-containing β-cells with or without a stabilizing-enhancing bile acid. Formed microcapsules were examined, for physical characteristics, and encapsulated cells were examined for survival, insulin release, and inflammatory profiles. Optimized microencapsulating parameters, using IGJVF, were: 1000 V voltage, 2500 Hz frequency, 1 mL/min flow rate, 3% w/v ionic-bath gelation concentration, and 20 min gelation time. Microcapsules showed good morphology and stability, and the encapsulated cells showed good survival, and insulin secretion, which was optimized by the bile acid. Deployed IGVJF-based microencapsulating parameters utilizing stability-enhancing bile acid produced best microcapsules with best pancreatic β-cells functions and survival rate, which, suggests potential application in cell transplantation.

摘要

在先前的研究中,我们开发了一种新技术(离子凝胶振动射流法;IGJVF),用于包裹胰岛β细胞,以实现胰岛素的体内递送及糖尿病治疗。所制备的微胶囊形态良好,但细胞功能有限。因此,本研究旨在通过整合电极张力、结合高内部振动、射流聚合物流速、离子浴凝胶浓度和凝胶化停留时间来优化IGJVF技术。该研究还利用微囊化分散液的双内/外喷嘴分段成分流来形成β细胞微胶囊。此外,添加了一种微胶囊稳定胆汁酸,并对微胶囊的稳定性和细胞功能进行了测定。筛选了基于Buchi的利用IGJVF技术的内置系统,以生产含或不含稳定增强胆汁酸的最佳含β细胞微胶囊。对形成的微胶囊进行物理特性检查,对包封的细胞进行存活、胰岛素释放和炎症特征检查。使用IGJVF优化的微囊化参数为:1000 V电压、2500 Hz频率、1 mL/min流速、3% w/v离子浴凝胶浓度和20分钟凝胶化时间。微胶囊显示出良好的形态和稳定性,包封的细胞显示出良好的存活率和胰岛素分泌,且胆汁酸对其有优化作用。利用增强稳定性的胆汁酸所采用的基于IGJVF的微囊化参数产生了具有最佳胰岛β细胞功能和存活率的最佳微胶囊,这表明其在细胞移植中具有潜在应用价值。

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