Sepsis is a life-threatening condition caused by a dysregulated host response to infection. The development of sepsis is associated with excessive nitric oxide (NO) production, which plays an important role in controlling vascular homeostasis. 7-nitroindazole (7-NI) is a selective inhibitor of neuronal nitric oxide synthase (NOS-1) with potential application for treating NO imbalance conditions. However, 7-NI exhibits a low aqueous solubility and a short plasma half-life. To circumvent these biopharmaceutical limitations, pegylated (NEPEG_7NI) and non-pegylated nanoemulsions (NENPEG_7NI) containing 7-NI were developed. This study evaluates the pharmacokinetic profiles and toxicological properties of 7-NI loaded into the nanoemulsions. After a single intravenous administration of the free drug and the nanoemulsions at a dose of 10 mg.kg⁻¹ in Wistar rats, 7-NI was widely distributed in the organs. The pharmacokinetic parameters of C_max, t_1/2, and AUC_0-t were significantly increased after administration of the NEPEG_7NI, compared to both free 7-NI and NENPEG_7NI (p < 0.05). No observable adverse effects were observed after administering the free 7-NI, NEPEG_7NI, or NENPEG_7NI in the animals after a single dose of up to 3.0 mg.kg⁻¹. The results indicated that 7-NI-loaded nanoemulsions are safe, constituting a promising approach to treating sepsis.

脓毒症是一种由宿主对感染反应失调引起的危及生命的疾病。脓毒症的发生与一氧化氮（NO）的过量产生有关，一氧化氮在控制血管稳态中发挥着重要作用。 7-硝基吲唑 (7-NI) 是神经元一氧化氮合酶 (NOS-1) 的选择性抑制剂，具有治疗 NO 失衡状况的潜在应用。然而，7-NI 的水溶性较低，血浆半衰期较短。为了规避这些生物制药限制，开发了含有 7-NI 的聚乙二醇化 (NEPEG _7NI ) 和非聚乙二醇化纳米乳液 (NENPEG _{7 NI} )。本研究评估了纳米乳剂中加载的 7-NI 的药代动力学特征和毒理学特性。 Wistar大鼠单次静脉注射游离药物和剂量为10 mg.kg ^-1的纳米乳后，7-NI在各器官中广泛分布。与游离7-NI和NENPEG _7NI相比，给予NEPEG _7NI后，C _max 、t _1/2和AUC _0-t的药代动力学参数显着增加（p < 0.05）。在单次剂量高达3.0 mg.kg ^-1后，对动物施用游离7-NI、NEPEG _7NI或NENPEG _7NI后，没有观察到可观察到的副作用。结果表明，7-NI 负载的纳米乳剂是安全的，是治疗脓毒症的一种有前途的方法。