Neuroscience Cluster, Department of Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia.
School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
J Pharm Pharmacol. 2017 Nov;69(11):1447-1457. doi: 10.1111/jphp.12800. Epub 2017 Aug 15.
This study was aimed to investigate the potential of formulated valproic acid-encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA).
Valproic acid-encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity, drug content, drug encapsulation efficiency). Further investigations were also conducted to estimate the drug release, cytotoxic profile, in-vitro blood-brain barrier (BBB) permeability, pharmacokinetic parameter and the concentration of VPA and VANE in blood and brain.
Physical characterisation confirmed that VANE was suitable for parenteral administration. Formulating VPA into nanoemulsion significantly reduced the cytotoxicity of VPA. In-vitro drug permeation suggested that VANEs crossed the BBB as freely as VPA. Pharmacokinetic parameters of VANE-treated rats in plasma and brain showed F3 VANE had a remarkable improvement in AUC, prolongation of half-life and reduction in clearance compared to VPA. Given the same extent of in-vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood. The brain bioavailability of VPA was improved by prolonging the half-life of VPA by encapsulating it within the nanoemulsion-T80.
Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA.
本研究旨在探讨载有丙戊酸的纳米乳（VANE）提高丙戊酸（VPA）脑内生物利用度的潜力。
制备并物理表征载有丙戊酸的纳米乳（渗透压、黏度、药物含量、药物包封效率）。进一步的研究还包括评估药物释放、细胞毒性、体外血脑屏障（BBB）通透性、药代动力学参数以及 VPA 和 VANE 在血液和脑组织中的浓度。
物理特性分析证实 VANE 适合于肠胃外给药。将 VPA 制成纳米乳可显著降低 VPA 的细胞毒性。体外药物渗透研究表明，VANEs 穿过 BBB 的能力与 VPA 一样强。VANE 处理的大鼠血浆和脑组织中的药代动力学参数显示，与 VPA 相比，F3 VANE 具有显著提高的 AUC、延长的半衰期和降低的清除率。鉴于 VPA 和 VANE 具有相同程度的体外 BBB 通透性，VANE 在脑组织中的生物利用度更高，这归因于 VANE 在血液中的浓度更高。通过将 VPA 包封在纳米乳-T80 中，可以延长 VPA 的半衰期，从而提高 VPA 的血浆和脑内生物利用度。
含有 VPA 的纳米乳减轻了 VPA 的细胞毒性，并提高了 VPA 肠胃外给药的血浆和脑内生物利用度。
