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用于调节变应性鼻炎小鼠模型免疫应答的含过敏原和姜黄素的速溶舌下纳米纤维的研制。

Development of fast-dissolving sublingual nanofibers containing allergen and curcumin for immune response modulation in a mouse model of allergic rhinitis.

机构信息

Immunology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Oct;397(10):7839-7856. doi: 10.1007/s00210-024-03139-y. Epub 2024 May 14.

Abstract

Curcumin (CUR) has been considered a potential therapeutic agent for allergic reactions due to its antioxidant and anti-inflammatory activities. Nanofibers have attracted increasing attention in drug delivery. The aim of this study was to investigate the combined therapeutic effects of curcumin and allergen in nanofiber-based treatments in order to increase the effectiveness of sublingual immunotherapy (SLIT) efficacy in a mouse model of allergic rhinitis. Nanofibers containing CUR (1.25% and 2.5%) and ovalbumin 2% (OVA) as an allergen were prepared via electrospinning and characterized. BALB/c mice were sensitized with OVA to the induced allergic rhinitis model. SLIT with free and/or nanofibers was carried out. IL-4, INF-γ, and IgE serum levels were measured using ELISA. Splenocyte proliferation was evaluated by the MTT assay. Lung and nasal histological examinations and nasal lavage fluid (NALF) cell counting were carried out. Nanofibers containing 1.25% CUR and 2% OVA were chosen as the optimal formulations. SLIT treatment with the CUR and OVA nanofiber co-administration led to a significantly decreased serum IgE. Nanofiber containing 2.5 µg of CUR/mouse combined with OVA nanofiber showed a significant decrease in IL-4 and an increase in IFN-γ compared to other groups. NALF assessment showed a significant decrease in specific cell and eosinophil counts in the treated nanofiber groups. The histopathological results of NAL in the optimal formulations were near normal, with diminished cellular infiltration and inflammation. Our findings suggest that co-sublingual administration of allergen and CUR nanofibers can be considered as potential immunomodulatory agents.

摘要

姜黄素(CUR)因其抗氧化和抗炎活性而被认为是治疗过敏反应的潜在治疗剂。纳米纤维在药物传递中受到越来越多的关注。本研究旨在研究基于纳米纤维的姜黄素和变应原联合治疗的联合治疗效果,以提高变应原舌下免疫疗法(SLIT)在过敏性鼻炎小鼠模型中的疗效。通过静电纺丝制备了含有 CUR(1.25%和 2.5%)和 2%卵清蛋白(OVA)作为变应原的纳米纤维,并对其进行了表征。BALB/c 小鼠用 OVA 致敏以诱导过敏性鼻炎模型。进行了游离和/或纳米纤维的 SLIT。通过 ELISA 测量血清 IL-4、INF-γ 和 IgE 水平。通过 MTT 测定评估脾细胞增殖。进行肺和鼻组织学检查和鼻洗液(NALF)细胞计数。选择含有 1.25%CUR 和 2%OVA 的纳米纤维作为最佳配方。CUR 和 OVA 纳米纤维共同给药的 SLIT 治疗导致血清 IgE 显著降低。与其他组相比,含 2.5µg CUR/只的纳米纤维与 OVA 纳米纤维联合显示出 IL-4 的显著降低和 IFN-γ 的增加。NALF 评估显示,在治疗的纳米纤维组中,特异性细胞和嗜酸性粒细胞计数显著减少。最佳配方中 NAL 的组织病理学结果接近正常,细胞浸润和炎症减少。我们的研究结果表明,变应原和 CUR 纳米纤维的共同舌下给药可以被认为是潜在的免疫调节药物。

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