Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia.
Drug Deliv. 2022 Aug 8;29(1):2671-2684. doi: 10.1080/10717544.2022.2110996.
Vinpocetine (VNP), a semisynthetic active pharmaceutical ingredient, is used for oral management of cerebrovascular diseases because of its ability to enhance the blood flow to the brain. However, despite that, the therapeutic application of VNP is restricted due to its reduced bioavailability and diminished brain levels that could be attributed to its low aqueous solubility, short half-life, and presystemic metabolism exposure. Accordingly, the goal of this work was to explore the ability of surface-tailored intranasal emulsomes to boost brain delivery of the drug. A 32 factorial design was implemented to explore the impact of phospholipid (PL) to solid lipid weight ratio, PL to cholesterol molar ratio, and type of solid lipid on vesicle size, zeta potential, drug entrapment, and release efficiency of the new developed VNP emulsomes. Tailoring of the optimized emulsomal surface formulation was performed using either cationization or PEGylation approaches to boost blood-brain barrier penetration. The pharmacokinetic assessment in rats showed significantly improved bioavailability of VNP emulsomal formulations compared to the oral market product. Additionally, surface-tailored emulsomes exhibited significantly higher brain levels compared to the optimized emulsomes. Based on these findings, the proposed surface-tailored emulsomes could be considered as a promising platform for achieving high brain levels of VNP following intranasal administration.
长春西汀（VNP）是一种半合成的活性药物成分，因其能够增加大脑的血流量，而被用于口服治疗脑血管疾病。然而，尽管如此，由于其生物利用度低、脑内水平降低，可能是由于其低水溶性、半衰期短和预先的系统代谢暴露，VNP 的治疗应用受到限制。因此，这项工作的目的是探索经表面修饰的鼻内乳剂增强药物脑内递送的能力。采用 32 因素设计来研究磷脂（PL）与固体脂质重量比、PL 与胆固醇摩尔比以及固体脂质类型对囊泡大小、ζ电位、药物包封率和新开发的 VNP 乳剂释放效率的影响。通过阳离子化或 PEG 化方法对优化的乳剂表面配方进行修饰，以增强血脑屏障穿透性。在大鼠中的药代动力学评估表明，与口服市售产品相比，VNP 乳剂制剂的生物利用度显著提高。此外，经表面修饰的乳剂与优化的乳剂相比，脑内水平显著提高。基于这些发现，所提出的经表面修饰的乳剂可被视为经鼻内给药实现 VNP 高脑内水平的有前途的平台。
