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Transcutaneous Peptide Immunotherapy of Japanese Cedar Pollinosis Using Solid-in-Oil Nanodispersion Technology

机译:固体油纳米分散技术经皮肽免疫疗法治疗日本雪松花粉症

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摘要

Peptide immunotherapy is an attractive approach to relieve allergic symptoms such as rhinitis and asthma. Treatment of Japanse cedar pollinosis (Cryptomeria japonica; Cj), from which over one quarter of Japanese population suffer, is becoming a great concern. Recently, oral feeding of a peptide (7crp) consisting of seven immunodominant human T cell epitopes derived from two enzymes present in Cj pollen was demonstrated to have a benefit in treating Cj pollinosis. In this work, we aimed to apply a novel transcutaneous administration system as a simple and easy peptide delivery for an immunotherapy using a T cell epitope peptide. A modified 7crp peptide (7crpR) which contained triarginine linkers between each epitopes was designed to increase water solubility and was encapsulated in a unique solid-in-oil (S/O) nanodispersion. The S/O nanodispersion consists of a nano-sized peptide-surfactant complex dispersed in an oil vehicle. The S/O nanopartilces having an average diameter of 230 nm facilitated the permeation of the peptide 7crpR into the skin and suppressed serum total IgE and antigen-specific IgE levels in a Cj pollinosis mouse model. Transcutaneous administration of the T cell epitope peptide using the S/O nanodispersion system has potential for future simple and easy immunotherapy of Cj pollinosis.Electronic supplementary materialThe online version of this article (doi:10.1208/s12249-015-0333-x) contains supplementary material, which is available to authorized users.
机译:肽免疫疗法是缓解过敏性症状(如鼻炎和哮喘)的一种有吸引力的方法。日本雪松花粉病(Cryptomeria japonica; Cj)的治疗正引起人们的极大关注,日本四分之一的日本人口遭受这种疾病的困扰。近来,已证明口服饲喂由源自Cj花粉中两种酶的7种免疫显性人T细胞表位组成的肽(7crp)具有治疗Cj花粉病的益处。在这项工作中,我们旨在将一种新颖的经皮给药系统作为使用T细胞表位肽进行免疫治疗的简单易行的肽传递方法。修饰的7crp肽(7crpR)在每个表位之间包含三精氨酸接头,旨在提高水溶性,并封装在独特的油中固体(S / O)纳米分散体中。 S / O纳米分散体由分散在石油载体中的纳米级肽-表面活性剂复合物组成。在Cj花粉病小鼠模型中,平均直径为230 nm的S / O纳米颗粒促进了7crpR肽渗入皮肤,并抑制了血清总IgE和抗原特异性IgE水平。使用S / O纳米分散系统经皮施用T细胞表位肽具有潜在的未来简便易行的Cj花粉病免疫治疗的潜力。电子补充材料本文的在线版本(doi:10.1208 / s12249-015-0333-x)包含补充剂资料,可供授权用户使用。

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