Evaluation of nanoparticles as oral vehicles for immunotherapy against experimental peanut allergy

Evaluation of nanoparticles as oral vehicles for immunotherapy against experimental peanut allergy
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DOI:
10.1016/j.ijbiomac.2017.09.109
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发表时间:
2018-04-01
影响因子:
8.2
通讯作者:
Irache, Juan M.
Irache, Juan M.
中科院分区:
化学1区
文献类型:
--
作者:
Brotons-Canto, Ana;Gamazo, Carlos;Irache, Juan M.

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这项工作的目的是评估一种基于纳米颗粒的口服免疫疗法对实验性诱导的花生过敏的潜在应用。在这种情况下,含有主要致敏蛋白的烤花生提取物被包裹在聚酸酐纳米颗粒中。所得到的花生负载纳米颗粒(PE-NP)的平均尺寸约为150 nm,表面疏水性明显低于空纳米颗粒(NP)。这种低疏水性与猪肠黏液中比NP更高的体外扩散以及在体内到达肠上皮和Peyer’s补丁的重要能力密切相关。在花生预致敏CDI小鼠模型中评价PE-NP的免疫治疗能力。在完成三剂量的花生提取物治疗后,小鼠进行了腹腔内刺激,无论是游离的还是包裹在纳米颗粒中的。通过评估症状评分和小鼠肥大细胞蛋白酶-1水平(mMCPT-1)来评估过敏反应。PE-NP处理与mMCPT-1水平显著降低以及攻毒后存活率显著相关,证实了该配方对攻毒的保护作用。总之,这种基于纳米颗粒的配方可能是花生特异性免疫治疗的一种有价值的策略。(C) 2017 Elsevier B.V.版权所有
The aim of this work was to evaluate the potential application of an original oral immunotherapy, based on the use of nanoparticles, against an experimentally induced peanut allergy. In this context, a roasted peanut extract, containing the main allergenic proteins, were encapsulated into poly(anhydride) nanoparticles. The resulting peanut-loaded nanoparticles (PE-NP) displayed a mean size of about 150 nm and a significantly lower surface hydrophobicity than empty nanoparticles (NP). This low hydrophobicity correlated well with a higher in vitro diffusion in pig intestinal mucus than NP and an important in vivo capability to reach the intestinal epithelium and Peyer's patches.The immunotherapeutic capability of PE-NP was evaluated in a model of pre-sensitized CDI mice to peanut. After completing therapy of three doses of peanut extract, either free or encapsulated into nanoparticles, mice underwent an intraperitoneal challenge. Anaphylaxis was evaluated by means of assessment of symptom scores and mouse mast cell protease-1 levels (mMCPT-1). PE-NP treatment was associated with significant lower levels of mMCPT-1, and a significant survival rate after challenge, confirming the protective effect of this formulation against the challenge. In summary, this nanoparticle-based formulation might be a valuable strategy for peanut-specific immunotherapy. (C) 2017 Elsevier B.V. All rights reserved.