Preparation and Evaluation of Preventive Effects of Inhalational and Intraperitoneal Injection of Myrtenol Loaded Nano-Niosomes on Lung Ischemia-Reperfusion Injury in Rats.

Ischemia-reperfusion injury (IRI) is directly related to forming reactive oxygen species, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and cytokines. Niosomes are nanocarriers and an essential part of drug delivery systems. We aimed to investigate the effects of myrtenol's inhaled and intraperitoneal niosomal form, compared to its simple form, on lung ischemia reperfusion injury (LIRI). Wistar rats were divided into ten groups. Simple and niosomal forms of myrtenol were inhaled or intraperitoneally injected daily for one week prior to LIRI. We evaluated oxidative stress, apoptotic, and inflammatory indices, nitric oxide, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and histopathological indices. Pretreatment with simple and niosomal forms of myrtenol significantly inhibited the indices of pulmonary edema, pro-inflammatory cytokines and proteins, oxidant agents, nitric oxide, iNOS, apoptotic proteins, congestion of capillaries, neutrophil infiltration, and bleeding in the alveoli. Furthermore, myrtenol increased anti-inflammatory cytokines, anti-oxidants agents, eNOS, anti-apoptotic proteins and the survival time of animals. The niosomal form of myrtenol showed a more ameliorative effect than its simple form. The results showed the superior protective effect of the inhalation of myrtenol niosomal form against LIRI compared to its simple form and systemic use. (A); Timeline of the study, (B); heating method to make niosomes, (C); lung ischemia-reperfusion method, (D); bronchoalveolar fluid collection method, (E); summary of study findings. [Display omitted] • Inhalation and intraperitoneal injection of myrtenol in both simple and niosomal forms prevented increased edema, histopathological indices, and apoptotic cells in ischemia-reperfusion-induced lung injury in rats. • Inhalation and intraperitoneal administration of myrtenol in both forms prevented the increase in oxidant agents and pro-inflammatory cytokines and the decrease in antioxidants and anti-inflammatory cytokines induced by ischemia-reperfusion injury in rats. • The niosomal form of myrtenol was more potent than the simple form in mitigating ischemia-reperfusion-induced lung injury in rats. [ABSTRACT FROM AUTHOR]