Pharmacokinetics, biodistribution, and in vivo toxicity of 7-nitroindazole loaded in pegylated and non-pegylated nanoemulsions in rats.

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 _{7 NI} ) 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.
Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest.
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