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维生素 D 负载纳米乳剂在哮喘模型中的药理学和药代动力学研究。

Pharmacological and pharmacokinetic studies with vitamin D-loaded nanoemulsions in asthma model.

作者信息

Wei-hong Tang, Min-chang Guan, Zhen Xu, Jie Sun

机构信息

Taizhou Enze Medical Center Luqiao Hospital, Zhejiang, 318050, People's Republic of China.

出版信息

Inflammation. 2014 Jun;37(3):723-8. doi: 10.1007/s10753-013-9790-0.

DOI:10.1007/s10753-013-9790-0
PMID:24326945
Abstract

Vitamin D (VD) was studied for its anti-inflammatory activities with prepared VD-loaded nanoemulsions (VDNM) in ovalbumin-induced asthmatic mice in this paper. In this study, we prepared VDNM for the delivery of VD from the established composition of solid self-emulsifying drug delivery systems (sSEDDS) by spray-drying technique and evaluated its bioavailability (BA) and anti-inflammatory activities in experimental allergic asthma. After the mice were treated orally with VD or VDNM, the plasma 25(OH) D levels, polymorphonuclear cells, tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), total antioxidant activity, and C3 and C4 complement protein levels were studied, respectively. Treatment with VDNM reduced MPO activity, oxidative stress, C3 protein level, O2(-) level as well as the production of IL-1β and TNF-α. Pharmacokinetic studies showed that a significant increase in the maximum concentration (Cmax) and AUC0→24 h were observed in VDNM group when compared with VD group (P < 0.01). The result revealed that VDNM led to an improvement in oral BA of VD in a murine ovalbumin-induced asthma model. These data provided an important proof that VDNM might be a new potential therapy for the management of asthma in humans.

摘要

本文研究了维生素D(VD)负载纳米乳剂(VDNM)在卵清蛋白诱导的哮喘小鼠中的抗炎活性。在本研究中,我们通过喷雾干燥技术从已确定的固体自乳化药物递送系统(sSEDDS)组成中制备了用于递送VD的VDNM,并评估了其在实验性过敏性哮喘中的生物利用度(BA)和抗炎活性。在用VD或VDNM口服治疗小鼠后,分别研究了血浆25(OH)D水平、多形核细胞、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、总抗氧化活性以及C3和C4补体蛋白水平。用VDNM治疗可降低MPO活性、氧化应激、C3蛋白水平、O2(-)水平以及IL-1β和TNF-α的产生。药代动力学研究表明,与VD组相比,VDNM组的最大浓度(Cmax)和AUC0→24 h显著增加(P < 0.01)。结果表明,在小鼠卵清蛋白诱导的哮喘模型中,VDNM可提高VD的口服生物利用度。这些数据提供了一个重要证据,即VDNM可能是一种治疗人类哮喘的新的潜在疗法。

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