Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles.
Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles.
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DOI：
10.2147/ijn.s71543
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发表时间：
2014
影响因子：
8
通讯作者：
Sahudin S
中科院分区：
文献类型：
--
作者：
Hussain Z;Katas H;Mohd Amin MC;Kumolosasi E;Sahudin S
特应性皮炎是一种慢性、非接触性和渗出性疾病，伴有血管周围免疫介质的渗透，包括T辅助细胞(1型辅助细胞/2型辅助细胞)、肥大细胞和免疫球蛋白E。本研究探讨了氢化可的松(HC)纳米粒(NP)经皮给药的免疫调节和组织学效应。在这项研究中，HC是最弱的局部糖皮质激素，作为壳聚糖纳米粒经皮给药。采用NC/NGA小鼠模型，评价了NP-HC对2，4-二硝基氟苯诱导的特应性皮炎(AD)样皮肤损伤的药理和免疫学作用。体内Dino-Lite®显微镜评估显示，以NP为基础的配方显示出显著的降低AD病理特征(皮炎指数，3.0)的能力。由于一系列免疫病理事件的中断，包括免疫球蛋白E的产生，组胺的释放，以及受试动物血清和皮肤中前列腺素-E2和血管内皮生长因子-α的表达，以NP为基础的局部制剂预期具有抑制AD的活性。对AD样皮损中细胞因子表达的分析进一步表明，NP制剂抑制了NC/NGA小鼠血清和皮肤匀浆中IL-4、IL-5、IL-6、IL-13、IL-12p70、干扰素-γ和肿瘤坏死因子-α的病理表达。此外，我们的组织学结果表明，基于NP的配方抑制了成纤维细胞的渗透和弹性纤维的断裂，进一步支持了这些配方在维持弹性结缔组织完整性方面的临床重要性。目前的研究表明，NP介导的HC经皮给药可以被认为是一种有效的皮炎治疗方法。
Atopic dermatitis is a chronic, noncontiguous, and exudative disorder accompanied by perivascular infiltration of immune mediators, including T-helper (Type 1 helper/Type 2 helper) cells, mast cells, and immunoglobulin E. The current study explores the immunomodulatory and histological effects of nanoparticle (NP)-based transcutaneous delivery of hydrocortisone (HC). In this study, HC, the least potent topical glucocorticoid, was administered transcutaneously as chitosan NPs. The pharmacological and immunological effects of the NP-based HC delivery on the alleviation of 2,4-dinitrofluorobenzene-induced atopic dermatitis (AD)-like skin lesions were evaluated using the NC/Nga mouse model. In vivo Dino-Lite® microscopic assessment revealed that the NP-based formulation displayed a remarkable ability to reduce the severity of the pathological features of AD (dermatitis index, 3.0). The AD suppressive activity of the NP-based topical formulation was expected owing to the interruption of a series of immunopathological events, including the production of immunoglobulin E, release of histamine, and expression of prostaglandin-E2 and vascular endothelial growth factor-α in the sera and skin of the tested animals. Analysis of the cytokine expression in AD-like skin lesions further revealed that the NP-based formulation inhibited the pathological expression of interleukin (IL)-4, IL-5, IL-6, IL-13, IL-12p70, interferon-γ, and tumor necrosis factor-α in serum and skin homogenates of NC/Nga mice. Further, our histological findings indicated that the NP-based formulation inhibited fibroblast infiltration and fragmentation of elastic fibers, further supporting the clinical importance of these formulations in maintaining the integrity of elastic connective tissues. The current investigation suggests that NP-mediated transcutaneous delivery of HC could be considered an effective therapeutic approach to manage dermatitis.