负载维生素E的白藜芦醇纳米乳剂用于脑靶向治疗帕金森病,通过减轻氧化应激。
Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson's disease by reducing oxidative stress.
作者信息
Pangeni Rudra, Sharma Shrestha, Mustafa Gulam, Ali Javed, Baboota Sanjula
机构信息
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, New Delhi-110062, India.
出版信息
Nanotechnology. 2014 Dec 5;25(48):485102. doi: 10.1088/0957-4484/25/48/485102. Epub 2014 Nov 13.
Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson's disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml(-1) of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.
白藜芦醇是一种有效的天然抗氧化剂,具有广泛的药理活性,但其口服生物利用度很低,因为它在肝脏和体循环前有广泛的代谢。本研究的目的是使用维生素E:sefsol(1:1)作为油相、吐温80作为表面活性剂和肉豆蔻酸异丙酯作为助表面活性剂来制备一种动力学稳定的纳米乳剂(油包水型),以更好地治疗帕金森病。通过自发乳化法制备纳米乳剂,随后进行高压均质。构建三元相图以确定纳米乳剂区域。对制备的制剂进行了粒径、ζ电位、折射率、粘度、表面形态以及体外和离体释放研究。含有150 mg ml(-1)白藜芦醇的均质制剂显示出球形颗粒,平均粒径为102 ± 1.46 nm,最低多分散指数为0.158 ± 0.02,最佳ζ电位值为 -35 ± 0.02。预均质白藜芦醇悬浮液、预均质纳米乳剂和后均质纳米乳剂在24小时后的药物累积释放百分比分别为24.18 ± 2.30%、54.32 ± 0.95%和88.57 ± 1.92%。离体释放也显示在24小时时药物累积释放百分比为85.48 ± 1.34%。通过DPPH测定法测定的抗氧化活性表明优化后的制剂具有高清除效率。药代动力学研究表明,经鼻给药优化后的纳米乳剂后,脑中药物浓度较高(脑/血比:2.86 ± 0.70)。组织病理学研究表明,给予白藜芦醇纳米乳剂的组中退行性变化减少。白藜芦醇纳米乳剂治疗组中谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平显著升高,丙二醛(MDA)水平显著降低。