Nitric oxide (NO) deficiency is often associated with several acute and chronic diseases. NO donors and especially S-nitrosothiols such as S-nitrosoglutathione (GSNO) have been identified as promising therapeutic agents. Although their permeability through the intestinal barrier have recently be proved, suitable drug delivery systems have to be designed for their oral administration. This is especially challenging due to the physico-chemical features of these drugs: high hydrophilicity and high lability. In this paper, three types of particles were prepared with an Eudragit® polymer: nanoparticles and microparticles obtained with a water-in-oil-in-water emulsion/evaporation process versus microparticles obtained with a solid-in-oil-in-water emulsion/evaporation process. They had a similar encapsulation efficiency (around 30%), and could be freeze-dried then be stored at least one month without modification of their critical attributes (size and GSNO content). However, microparticles had a slightly slower in vitro release of GSNO than nanoparticles, and were able to boost by a factor of two the drug intestinal permeability (Caco-2 model). Altogether, this study brings new data about GSNO intestinal permeability and three ready-to-use formulations suitable for further preclinical studies with oral administration.

一氧化氮（NO）缺乏症通常与几种急性和慢性疾病有关。NO供体，尤其是S-亚硝基硫醇，例如S-亚硝基谷胱甘肽（GSNO），已被确定为有前途的治疗剂。尽管最近已经证明了它们可通过肠屏障的渗透性，但必须为口服给药设计合适的药物输送系统。由于这些药物的物理化学特征，这尤其具有挑战性：高亲水性和高不稳定性。在本文中，使用Eudragit®聚合物制备了三种类型的颗粒：通过水包油包水型乳液/蒸发工艺获得的纳米颗粒和微粒与水包油型固体乳液/蒸发工艺获得的微粒。它们具有相似的封装效率（大约30％），可以冷冻干燥然后保存至少一个月，而无需更改其关键属性（大小和GSNO含量）。但是，微粒在体外的GSNO释放速度比纳米微粒要慢一些，并且能够将药物的肠道渗透性提高两倍（Caco-2模型）。总而言之，这项研究带来了有关GSNO肠通透性的新数据，以及三种适用于口服给药进一步临床前研究的现成制剂。