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静电纺丝聚琥珀酰亚胺 - 多巴胺共轭物的表征及其对细胞活力和摄取的影响

Characterization of Electrospun Polysuccinimide-Dopamine Conjugates and Effect on Cell Viability and Uptake.

作者信息

Tóth Krisztina, S Nagy Krisztina, Güler Zeliha, Juhász Ákos György, Pállinger Éva, Varga Gábor, Sarac A Sezai, Zrínyi Miklós, Jedlovszky-Hajdú Angéla, Juriga Dávid

机构信息

Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary.

Department of Oral Biology, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary.

出版信息

Macromol Biosci. 2023 Mar;23(3):e2200397. doi: 10.1002/mabi.202200397. Epub 2023 Jan 17.

Abstract

Biocompatible nanofibrous systems made by electrospinning have been studied widely for pharmaceutical applications since they have a high specific surface and the capability to make the entrapped drug molecule amorphous, which increases bioavailability. By covalently conjugating drugs onto polymers, the degradation of the drug as well as the fast clearance from the circulation can be avoided. Although covalent polymer-drug conjugates have a lot of advantages, there is a lack of research focusing on their nano-formulation by electrospinning. In this study, polysuccinimide (PSI) based electrospun fibrous meshes conjugated with dopamine (DA) are prepared. Fiber diameter, mechanical properties, dissolution kinetics and membrane permeability are thoroughly investigated, as these are crucial for drug delivery and implantation. Dopamine release kinetics prove the prolonged release that influenced the viability and morphology of periodontal ligament stem cells (PDLSCs) and SH-SY5Y cells. The presence of dopamine receptors on both cell types is also demonstrated and the uptake of the conjugates is measured. According to flow cytometry analysis, the conjugates are internalized by both cell types, which is influenced by the chemical structure and physical properties. In conclusion, electrospinning of PSI-DA conjugates alters release kinetics, meanwhile, conjugated dopamine can play a key role in cellular uptake.

摘要

通过静电纺丝制备的生物相容性纳米纤维系统因其具有高比表面积以及能使包封的药物分子呈无定形从而提高生物利用度,而在药物应用方面受到广泛研究。通过将药物共价连接到聚合物上,可以避免药物降解以及从循环系统中快速清除。尽管共价聚合物 - 药物缀合物有很多优点,但缺乏关于通过静电纺丝制备其纳米制剂的研究。在本研究中,制备了与多巴胺(DA)共轭的基于聚琥珀酰亚胺(PSI)的静电纺丝纤维网。对纤维直径、力学性能、溶解动力学和膜渗透性进行了全面研究,因为这些对于药物递送和植入至关重要。多巴胺释放动力学证明了其缓释特性,这影响了牙周膜干细胞(PDLSCs)和SH - SY5Y细胞的活力和形态。还证明了两种细胞类型上多巴胺受体的存在,并测量了缀合物的摄取。根据流式细胞术分析,缀合物被两种细胞类型内化,这受化学结构和物理性质的影响。总之,PSI - DA缀合物的静电纺丝改变了释放动力学,同时,共轭多巴胺在细胞摄取中起关键作用。

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