Khederzadeh Aram, Ebrahimnejad Pedram, Seyedabadi Mohammad, Babaei Amirhossein, Amiri Fereshteh Talebpour, Aslani Nasim, Mojarad-Jabali Solmaz, Mohammadi Hamidreza
Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Mazandaran Province, Farah Abad Road, P3MV+78R, PO Box- 48175/861, Sari, Iran.
Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Faculty of Pharmacy, Mazandaran Province, Farah Abad Road, P3MV+78R, PO Box- 48175/861, Sari, Iran.
Toxicol Res (Camb). 2024 Nov 5;13(6):tfae181. doi: 10.1093/toxres/tfae181. eCollection 2024 Dec.
Paraquat (PQ), a widely used non-selective herbicide, induces severe lung toxicity by promoting cell death and tissue necrosis through the generation of reactive oxygen species (ROS) and free radicals. This study aimed to develop and evaluate novel niosomal nanoparticles (NPs) encapsulating curcumin and piperine to mitigate PQ-induced acute pulmonary toxicity in Balb/c mice.
The NPs were prepared using non-ionic surfactants and cholesterol via the thin film hydration method.
Characterization revealed high encapsulation efficiency (>85%), proper particle sizes (264-286 nm), narrow polydispersity index (PDI) (0.19 ± 0.04 to 0.23 ± 0.02), and good stability over 90 days. Thermal analysis confirmed successful encapsulation of curcumin and piperine within the niosomal NPs. In vivo studies showed that PQ exposure significantly elevated ROS, lipid peroxidation (LPO), and protein carbonylation (PC) levels, while reducing glutathione (GSH) levels and impairing mitochondrial function (P < 0.001). However, co-treatment with curcumin- and piperine-loaded niosomal NPs effectively reversed these effects (P < 0.001), improving mitochondrial function.
The combined formulation of curcumin and piperine in niosomal NPs offers a promising therapeutic strategy for treating PQ-induced pulmonary toxicity, likely due to enhanced bioavailability and potent antioxidant activity.
百草枯（PQ）是一种广泛使用的非选择性除草剂，通过产生活性氧（ROS）和自由基促进细胞死亡和组织坏死，从而诱发严重的肺毒性。本研究旨在开发和评估包裹姜黄素和胡椒碱的新型脂质体纳米颗粒（NPs），以减轻PQ诱导的Balb/c小鼠急性肺毒性。
通过薄膜水化法使用非离子表面活性剂和胆固醇制备NPs。
表征显示包封率高（>85%）、粒径合适（264 - 286 nm）、多分散指数（PDI）窄（0.19±0.04至0.23±0.02），并且在90天内具有良好的稳定性。热分析证实姜黄素和胡椒碱成功包封在脂质体NPs内。体内研究表明，暴露于PQ会显著提高ROS、脂质过氧化（LPO）和蛋白质羰基化（PC）水平，同时降低谷胱甘肽（GSH）水平并损害线粒体功能（P < 0.001）。然而，与负载姜黄素和胡椒碱的脂质体NPs联合处理可有效逆转这些效应（P < 0.001），改善线粒体功能。
脂质体NPs中姜黄素和胡椒碱的联合制剂为治疗PQ诱导的肺毒性提供了一种有前景的治疗策略，这可能归因于提高的生物利用度和强大的抗氧化活性。
