Raeisi Estabragh Mohammad Amin, Pardakhty Abbas, Ahmadzadeh Saeid, Dabiri Shahriar, Malekpour Afshar Reza, Farajli Abbasi Mohammad
Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.
Adv Pharm Bull. 2022 May;12(3):541-549. doi: 10.34172/apb.2022.058. Epub 2021 Sep 12.
Free radicals such as hydroxyl and peroxide are contributing factors to neuronal destruction in cerebral ischemia. Alpha-lipoic acid (ALA) is one of the potent known antioxidants. Preparation of ALA niosomes allows IV injection and can increase bioavailability and penetration into the central nervous system (CNS). Film hydration method was used to prepare different niosomes composed of Span®, Tween®, and cholesterol at different molar ratio. ALA and niosome-forming compounds were dissolved in chloroform, before removing the organic solvent by rotary evaporator. Animals were randomly divided into four groups: Sham, control group, intravenous (IV) injection of empty niosomes plus intraperitoneal (IP) injection of ALA solution, and finally, IV injection of ALA niosomes. Rats were subjected to deep anesthesia before inducing cerebral ischemia, then, their internal common carotid arteries were clamped for 15 min and reperfusion was done for 30 min. Niosomal ALA was injected intravenously just before declamping. Mean volume diameter of the prepared niosomes was between 4.36 ± 0.82 and 19.95 ± 1.21 μm in different formulations. Encapsulation efficiency percent (EE%) of ALA in the selected formulation, Span60/Tween60/cholesterol (35:35:30 molar ratio), was 94.5 ± 0.2, and 59.27 ± 5.61% of ALA was released after 4h. In the niosomal group, the rate of reduction in complications of cerebral ischemia such as histopathologic changes and acute damage (from score 3 to 1) in CNS was higher than other groups. The obtained results show that niosomes can be used as effective drug delivery systems for ALA in cerebral ischemia.
诸如羟基和过氧化物等自由基是脑缺血中神经元破坏的促成因素。α-硫辛酸（ALA）是已知的强效抗氧化剂之一。制备ALA脂质体可进行静脉注射，并能提高生物利用度以及进入中枢神经系统（CNS）的渗透率。采用薄膜水化法，以不同摩尔比制备了由司盘®、吐温®和胆固醇组成的不同脂质体。将ALA和形成脂质体的化合物溶解于氯仿中，然后用旋转蒸发仪除去有机溶剂。动物被随机分为四组：假手术组、对照组、静脉注射空脂质体加腹腔注射ALA溶液组，以及最后静脉注射ALA脂质体组。在诱导脑缺血前，大鼠接受深度麻醉，然后夹闭其颈内动脉15分钟，并进行30分钟的再灌注。在松开动脉夹之前，静脉注射脂质体ALA。所制备脂质体的平均体积直径在不同配方中为4.36±0.82至19.95±1.21μm之间。在选定配方司盘60/吐温60/胆固醇（摩尔比35:35:30）中，ALA的包封率（EE%）为94.5±0.2，4小时后59.27±5.61%的ALA被释放。在脂质体组中，脑缺血并发症如组织病理学变化和中枢神经系统急性损伤（评分从3降至1）的减少率高于其他组。所得结果表明，脂质体可作为ALA在脑缺血中的有效药物递送系统。
