Pharmaceutical Technology Department, National Research Centre, Dokki, Cairo, Egypt.
Inorganic Chemistry Department, National Research Centre, Dokki, Cairo, Egypt.
Int J Pharm. 2018 Aug 25;547(1-2):83-96. doi: 10.1016/j.ijpharm.2018.05.038. Epub 2018 May 17.
The objective of this study was to innovate an effective oral sustained release hepatoprotective formula for - the water soluble drug - caffeine. Caffeine is rapidly absorbed and eliminated which dictates frequent administration to achieve adequate therapeutic effect. A w/o Pickering emulsion incorporating caffeine in the internal phase was primed. It contained wheat germ oil and was stabilized by synthesized magnesium oxide nanoparticles (MgO NPs). Components selection was based on their antioxidant, hepatoprotective and anticarcinogenic effects. The MgO NPs were prepared via sol-gel method, and then were characterized using X-ray diffractometry, transmission electron microscopy, contact angle and cytotoxicity. The Pickering emulsion formula stabilized by MgO NPs (F1) was compared to another stabilized by conventional MgO particles (F2). Both were evaluated regarding droplet size, stability and caffeine release. F1 was stable against phase separation for a 2 months period. Its droplets mean size was 665.9 ± 90 nm. F1 afforded sustained release for caffeine that reached 70% within 48 h that followed zero order kinetics. 100 ppm of F1 showed nearly 36% growth inhibition of hepatocellular carcinoma (HEPG2). In vivo and histopathalogical evaluations were conducted on CCl intoxicated rats. Biochemical analysis for liver enzymes - (ALT and AST), oxidative stress biomarkers and the inflammation marker (protein kinase C) - revealed that the selected formula elicited significant hepatoprotection. This formula acted as an economical approach to multiple therapy and afforded safe effective sustained level for caffeine.
本研究旨在创新一种有效的口服缓释保肝配方，用于水溶性药物——咖啡因。咖啡因吸收迅速，消除迅速，这就要求频繁给药以达到足够的治疗效果。我们制备了一种含有咖啡因的 W/O Pickering 乳液，内部水相含有小麦胚芽油，并由合成的氧化镁纳米颗粒 (MgO NPs) 稳定。成分的选择基于它们的抗氧化、保肝和抗癌作用。采用溶胶-凝胶法制备 MgO NPs，并用 X 射线衍射仪、透射电子显微镜、接触角和细胞毒性对其进行表征。用 MgO NPs 稳定的 Pickering 乳液配方（F1）与用传统 MgO 颗粒稳定的配方（F2）进行了比较。我们评估了它们的粒径、稳定性和咖啡因释放。F1 能够稳定地防止相分离长达 2 个月。其液滴平均粒径为 665.9±90nm。F1 能够持续释放咖啡因，48 小时内达到 70%，遵循零级动力学。F1 的浓度为 100ppm 时，对肝癌细胞（HEPG2）的抑制率接近 36%。对 CCl 中毒大鼠进行了体内和组织病理学评价。对肝脏酶（ALT 和 AST）、氧化应激生物标志物和炎症标志物（蛋白激酶 C）进行生化分析，结果表明所选配方具有显著的保肝作用。这种配方是一种经济有效的多疗法，并能提供安全有效的咖啡因持续水平。
