Department of Pharmaceutics, National Organization for Drug Control and Research, Giza, 12654, Egypt.
Faculty of Pharmacy, Department of Pharmaceutics and Industrial Pharmacy, Cairo University, Cairo, 11562, Egypt.
J Pharm Sci. 2020 Jul;109(7):2213-2223. doi: 10.1016/j.xphs.2020.03.030. Epub 2020 Apr 4.
Vascular dementia is a condition characterized by a wretched cerebral circulation which can lead to memory loss. Vinpocetine showed ability to promote the cerebral circulation and depict neuroprotective impacts. However, it suffers from poor bioavailability and requires frequent daily dosing which is not suitable for dementia patients. In our study, these limitations were overcome by the prolonged direct delivery of vinpocetine to the brain utilizing an intranasal in situ hexosomal gel. A central composite design was utilized and the optimum dispersion (consisting of 15% w/w of oleic acid and 5% w/w of pluronic F127) was loaded in an in situ gel system using gellan gum with 1% w/v. The optimized Formulae achieved a controlled drug release over 24 h and the pharmacokinetic data revealed that the C and AUC in the rats' brain after the intranasal application of the dispersion and in situ gel were significantly higher relative to the vinpocetine solution applied intravenously at the same dose. The potential of both formulae to deliver vinpocetine to the brain directly through the intranasal route was confirmed by the high BTE% of 370.97% and 480.70% and the high DTP% of 73.04% and 79.19% for the dispersion and in situ gel, respectively.
血管性痴呆是一种以脑循环不良为特征的疾病，可导致记忆力减退。长春西汀具有促进脑循环和表现出神经保护作用的能力。然而，它的生物利用度差，需要每天频繁给药，这对痴呆症患者来说并不适用。在我们的研究中，通过利用鼻腔内原位六面体凝胶将长春西汀长时间直接递送至大脑，克服了这些限制。采用中心组合设计，将最佳分散体（由 15%w/w 的油酸和 5%w/w 的泊洛沙姆 F127 组成）加载到原位凝胶系统中，使用 1%w/v 的结冷胶。优化后的配方实现了 24 小时的药物控释，药代动力学数据显示，与静脉注射相同剂量的长春西汀溶液相比，经鼻应用该分散体和原位凝胶后，大鼠大脑中的 C 和 AUC 显著升高。两种配方通过鼻腔途径直接将长春西汀递送至大脑的能力得到了确认，其 BTE%分别为 370.97%和 480.70%，DTP%分别为 73.04%和 79.19%。
