Ebrahimi Hossein, Kazem Nezhad Sajjad, Farmoudeh Ali, Babaei Amirhossein, Ebrahimnejad Pedram, Akbari Esmaeil, Siahposht-Khachaki Ali
Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Science, Sari, Iran.
Student Research Committee, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran.
Eur J Pharm Biopharm. 2022 Dec;181:122-135. doi: 10.1016/j.ejpb.2022.10.018. Epub 2022 Oct 25.
Following traumatic brain injury, inflammation, mitochondrial dysfunction, oxidative stress, ischemia, and energy crisis can cause mortality or long-term morbidity. As an activator of AMP-activated protein kinase, metformin reduces the secondary injuries of traumatic brain injury by compensating for the lack of energy in damaged cells. But the blood-brain barrier prevents a hydrophilic drug such as metformin from penetrating the brain tissue. Solid lipid nanoparticles with their lipid nature can cross the blood-brain barrier and solve this challenge. so This study aimed to investigate the effect of metformin-loaded lipid nanoparticles (NanoMet) for drug delivery to the brain and reduce complications from traumatic brain injury.
Different formulations of NanoMet were designed by Box-Behnken, and after formulation, particle size, zeta potential, and entrapment efficiency were investigated. For in vivo study, Male rats were divided into eight groups, and except for the intact and sham groups, the other groups underwent brain trauma by the Marmarou method. After the intervention, the Veterinary Coma Scale, Vestibular Motor function, blood-brain barrier integrity, cerebral edema, level of inflammatory cytokines, and histopathology of brain tissue were assessed.
The optimal formula had a size of 282.2 ± 9.05 nm, a zeta potential of -1.65 ± 0.33 mV, and entrapment efficiency of 60.61 ± 6.09% which released the drug in 1400 min. Concentrations of 5 and 10 mg/kg of this formula improved the consequences of trauma.
This study showed that nanoparticles could help target drug delivery to the brain and apply the desired result.
创伤性脑损伤后，炎症、线粒体功能障碍、氧化应激、缺血和能量危机可导致死亡或长期发病。作为一种AMP激活蛋白激酶的激活剂，二甲双胍通过补偿受损细胞中能量的缺乏来减少创伤性脑损伤的继发性损伤。但血脑屏障会阻止二甲双胍这类亲水性药物穿透脑组织。具有脂质性质的固体脂质纳米粒能够穿过血脑屏障并解决这一难题。因此，本研究旨在探究负载二甲双胍的脂质纳米粒（纳米二甲双胍）用于药物脑内递送及减少创伤性脑损伤并发症的效果。
采用Box-Behnken设计不同配方的纳米二甲双胍，配方完成后，对粒径、zeta电位和包封率进行研究。在体内研究中，将雄性大鼠分为八组，除完整组和假手术组外，其他组采用 Marmarou 法造成脑损伤。干预后，评估兽用昏迷量表、前庭运动功能、血脑屏障完整性、脑水肿、炎症细胞因子水平和脑组织病理学。
最优配方的粒径为282.2±9.05nm，zeta电位为-1.65±0.33mV，包封率为60.61±6.09%，药物在1400分钟内释放。该配方5mg/kg和10mg/kg的浓度改善了创伤后果。
本研究表明纳米粒有助于将药物靶向递送至脑内并取得预期效果。
