M Soliman Sara, M Sheta Nermin, M M Ibrahim Bassant, M El-Shawwa Mohammad, M Abd El-Halim Shady
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, 6th of October University, Central Axis, Sixth of October City, Giza 12585, Egypt.
Department of Pharmacology, Medical Research Division, National Research Centre, Dokki, Giza 12622, Egypt.
Pharmaceutics. 2020 Jan 17;12(1):76. doi: 10.3390/pharmaceutics12010076.
Brain damage caused by cerebral ischaemia/reperfusion (I/R) can lead to handicapping. So, the present study aims to evaluate the prophylactic and therapeutic effects of geraniol in the form of intranasal polymeric mixed micelle (PMM) on the central nervous system in cerebral ischaemia/reperfusion (I/R) injury. A 3 factorial design was used to prepare and optimize geraniol PMM to investigate polymer and stabilizer different concentrations on particle size (PS) and percent entrapment efficiency (%EE). F3 possessing the highest desirability value (0.96), with a PS value of 32.46 ± 0.64 nm, EE of 97.85 ± 1.90%, and release efficiency of 59.66 ± 0.64%, was selected for further pharmacological and histopathological studies. In the prophylactic study, animals were classified into a sham-operated group, a positive control group for which I/R was done without treatment, and treated groups that received vehicle (plain micelles), geraniol oil, and geraniol micelles intranasally before and after I/R. In the therapeutic study, treated rats received geraniol oil and micelles after I/R. Evaluation of the effect of geraniol on behavior was done by activity cage and rotarod and the analgesic effect tested by hot plate. Anti-inflammatory activity was assessed by measuring interleukin β6, cyclooxygenase-2, hydrogen peroxide, and inducible nitric oxide synthase. Histopathogical examination of cerebral cortices was also done to confirm the results of a biochemical assay. Geraniol nanostructured polymeric mixed micelles showed an enhanced neuro-protective effect compared to geraniol oil, confirming that PMM via intranasal route could be an efficient approach for delivering geraniol directly to the brain through crossing the blood-brain barrier.
脑缺血/再灌注（I/R）引起的脑损伤可导致残疾。因此，本研究旨在评估香叶醇鼻内聚合物混合胶束（PMM）对脑缺血/再灌注（I/R）损伤中枢神经系统的预防和治疗作用。采用三因素设计制备并优化香叶醇PMM，以研究聚合物和稳定剂不同浓度对粒径（PS）和包封率（%EE）的影响。选择可取性值最高（0.96）的F3进行进一步的药理和组织病理学研究，其PS值为32.46±0.64nm，EE为97.85±1.90%，释放效率为59.66±0.64%。在预防性研究中，动物分为假手术组、未治疗进行I/R的阳性对照组以及在I/R前后经鼻接受载体（普通胶束）、香叶醇油和香叶醇胶束的治疗组。在治疗性研究中，治疗大鼠在I/R后接受香叶醇油和胶束。通过活动笼和转棒试验评估香叶醇对行为的影响，通过热板试验测试镇痛效果。通过测量白细胞介素β6、环氧化酶-2、过氧化氢和诱导型一氧化氮合酶评估抗炎活性。还对大脑皮层进行了组织病理学检查以证实生化分析结果。与香叶醇油相比，香叶醇纳米结构聚合物混合胶束显示出增强的神经保护作用，证实经鼻途径的PMM可能是一种通过血脑屏障将香叶醇直接递送至大脑的有效方法。
