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静电纺丝法制备用于牙髓治疗的地塞米松/环糊精包合物聚合物纤维。

Electrospinning of dexamethasone/cyclodextrin inclusion complex polymer fibers for dental pulp therapy.

机构信息

Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109, United States; Department of Restorative Dental Sciences, College of Dentistry, Jazan University, Jazan, 45142, Kingdom of Saudi Arabia.

Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109, United States.

出版信息

Colloids Surf B Biointerfaces. 2020 Jul;191:111011. doi: 10.1016/j.colsurfb.2020.111011. Epub 2020 Apr 7.

Abstract

Beta-cyclodextrin (β-CD) is an oligosaccharide commonly used to improve the aqueous solubility of lipophilic drugs (e.g., dexamethasone, DEX). Here we present the development of a drug delivery system to provide sustained release of DEX by β-CD-inclusion complex (IC) to amplify the mineralization capacity of stem cells from human-extracted deciduous teeth (SHEDs) as a potential direct pulp capping strategy. First, IC of DEX (DEX-CD-IC) was synthesized with β-CD. To confirm DEX-CD-IC complex formation, X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analyses were performed. XRD data indicated that IC formation was achieved due to formation of a new crystalline structure, whereas FTIR revealed the presence of the IC from the shifting of the peaks of each component in DEX-CD-IC. Then, electrospun poly(lactic-co-glycolic acid, PLGA) fibers (PLGA/DEX-CD-IC) were processed by varying the concentration of DEX-CD-IC (5%, 10 %, and 15 %). The release of DEX from fibers was determined by ultraperformance liquid chromatography for 28 days. Thanks to the solubility enhancement of DEX by IC, electrospun PLGA/DEX-CD-IC fibers released DEX in a more sustained fashion compared to PLGA/DEX fibers. No deleterious effect was found in terms of SHEDs' proliferation when cultured with or on electrospun fibers, regardless of the IC presence. Importantly, a more pronounced odontogenic differentiation was stimulated by electrospun fibers loaded with the lowest DEX-CD-IC concentration (5%), as a result of the sustained DEX release. In sum, PLGA/DEX-CD-IC fibers have great potential in vital dental pulp therapy, owing to its sustained DEX release, cytocompatibility, and odontogenic differentiation capacity.

摘要

β-环糊精(β-CD)是一种常用的寡糖,可提高疏水性药物(如地塞米松,DEX)的水溶性。在这里,我们开发了一种药物传递系统,通过β-CD 包合物(IC)提供 DEX 的持续释放,以放大人乳牙来源干细胞(SHED)的矿化能力,作为一种潜在的直接牙髓覆盖策略。首先,用β-CD 合成了 DEX 的 IC(DEX-CD-IC)。为了确认 DEX-CD-IC 复合物的形成,进行了 X 射线衍射(XRD)和傅里叶变换红外光谱(FTIR)分析。XRD 数据表明,由于形成了新的结晶结构,IC 的形成得以实现,而 FTIR 则表明从 DEX-CD-IC 中每个成分的峰的移动存在 IC。然后,通过改变 DEX-CD-IC 的浓度(5%、10%和 15%)来处理电纺聚(乳酸-共-乙醇酸,PLGA)纤维(PLGA/DEX-CD-IC)。通过超高效液相色谱法在 28 天内测定了纤维中 DEX 的释放。由于 IC 提高了 DEX 的溶解度,因此与 PLGA/DEX 纤维相比,电纺 PLGA/DEX-CD-IC 纤维以更持续的方式释放 DEX。无论 IC 是否存在,用或在电纺纤维上培养时,均未发现对 SHEDs 增殖有任何有害影响。重要的是,负载最低 DEX-CD-IC 浓度(5%)的电纺纤维刺激了更明显的成牙本质分化,这是由于 DEX 的持续释放。总之,由于其持续的 DEX 释放、细胞相容性和成牙本质分化能力,PLGA/DEX-CD-IC 纤维在有活力的牙髓治疗中具有很大的潜力。

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