Nanomedicine Research Group, Department of Pharmacy Quaid-i-Azam University, 45320 Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
Nanomedicine Research Group, Department of Pharmacy Quaid-i-Azam University, 45320 Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
Int J Pharm. 2023 Nov 5;646:123480. doi: 10.1016/j.ijpharm.2023.123480. Epub 2023 Oct 4.
Migraine is a progressive neurological condition often accompanied by nausea and vomiting. Various drugs have recently been used in the treatment of migraine, including sumatriptan (SUT). However, SUT has poor pharmacological effects mainly due to its reduced permeability, blood brain barrier (BBB) effect, half-life and bioavailability. Herein, we developed SUT loaded nano-ethosomes (SUT-NEs) for intranasal (IN) delivery, after their incorporation into chitosan based mucoadhesive gel (SUT-NEsG). The observed mean particle size of SUT-NEs was 109.45 ± 4.03 nm with spherical morphology, mono dispersion (0.191 ± 0.001), negatively charged (-20.90 ± 1.98 mV) and with excellent entrapment efficiency (96.90 ± 1.85 %). Fourier-transform infrared (FTIR) spectra have depicted the compatibility of the components. Moreover, SUT-NEsG was homogeneous having suitable viscosity and mucoadhesive strength. In vitro release and ex vivo permeation analysis showed sustained release and improved permeation of the SUT-NEsG, respectively. Additionally, histopathological studies of nasal membrane affirmed the safety of SUT-NEsG after IN application. In vivo pharmacokinetic study demonstrated improved brain bioavailability of SUT-NEsG as compared to orally administered sumatriptan solution (SUT-SL). Furthermore, significantly enhanced pharmacological effect of SUT-NEsG was observed in behavioral and biochemical analysis, immunohistochemistry for NF-κB, and enzyme linked immuno assay (ELISA) for IL-1β and TNF-α in Nitroglycerin (NTG) induced migraine model. It can be concluded that migraine may be successfully managed through IN application of SUT-NEsG owing to the direct targeted delivery to the brain.
偏头痛是一种进行性的神经系统疾病，常伴有恶心和呕吐。最近，各种药物被用于偏头痛的治疗，包括舒马曲坦（SUT）。然而，SUT 的药理学效果较差，主要是由于其渗透性降低、血脑屏障（BBB）效应、半衰期和生物利用度。在此，我们开发了 SUT 负载的纳米乙氧基醇（SUT-NEs），用于经鼻（IN）给药，然后将其整合到壳聚糖基粘膜粘附凝胶（SUT-NEsG）中。观察到的 SUT-NEs 的平均粒径为 109.45±4.03nm，呈球形形态，单分散性（0.191±0.001），带负电荷（-20.90±1.98mV），包封效率优异（96.90±1.85%）。傅里叶变换红外（FTIR）光谱描述了各成分的兼容性。此外，SUT-NEsG 是均匀的，具有合适的粘度和粘膜粘附强度。体外释放和离体渗透分析表明，SUT-NEsG 分别具有持续释放和改善的渗透性能。此外，鼻膜的组织病理学研究证实了 IN 应用后 SUT-NEsG 的安全性。体内药代动力学研究表明，与口服舒马曲坦溶液（SUT-SL）相比，SUT-NEsG 可改善大脑的生物利用度。此外，在硝酸甘油（NTG）诱导的偏头痛模型中，SUT-NEsG 的行为和生化分析、NF-κB 的免疫组化以及白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的酶联免疫吸附试验（ELISA）均观察到 SUT-NEsG 的显著增强的药理作用。可以得出结论，通过 IN 应用 SUT-NEsG 可能成功管理偏头痛，因为它可以直接靶向递送到大脑。
