Harisa Gamaleldin I, Alomrani Abdullah H, Badran Mohamed M
Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia; Department of Biochemistry, College of Pharmacy, Al-Azhar University (Boys), Nasr City, Cairo, Egypt.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia; Nanomedicine unit (NMU-KSU), College of Pharmacy, King Saud University, Saudi Arabia.
Eur J Pharm Sci. 2017 Jan 1;96:62-71. doi: 10.1016/j.ejps.2016.09.004. Epub 2016 Sep 7.
This study aimed to investigate the effect of simvastatin (SV) loaded nanostructured lipid carriers (SV loaded NLCs) on atherogenic index (AI), erythrocytes membrane lipid and antioxidant/pro-oxidant status in hyperlipidemic rats. SV loaded NLCs were successfully prepared with desired nano-particles size, spherical shape, high encapsulation efficiency (EE %) and sustained SV release. The results of biological studies revealed that administration of SV loaded NLCs to rats increased SV bioavailability compared to SV suspension. Intraperitoneal injection of tyloxapol as hyperlipidemic agent induces a significant increase of plasma AI, uric acid, lipid peroxidation and protein oxidation. While, plasma total antioxidant capacity and paraoxonase-1 activity were significantly decreased. Moreover, tyloxapol induced-hyperlipidemia increases erythrocyte's membrane cholesterol and deteriorates erythrocyte's antioxidant enzyme activity, GSH/GSSG ratio and NO level However, the propagation of erythrocyte's pro-oxidant activity and hemolysis was observed. On the contrast, the treatment of these rats with SV loaded NLCs improved the measured parameters compared to rats received SV suspension and hyperlipidemic rats. The predominant effect of SV loaded NLCs may be attributed to the enhancement of absorption, prolonged duration and improvement of bioavailability of SV. Accordingly, SV loaded NLCs showed advantageous effects on the blood lipid levels and atherogenic risk of erythrocytes in hyperlipidemic conditions compared to SV suspension.
本研究旨在探讨载有辛伐他汀（SV）的纳米结构脂质载体（载SV的NLCs）对高脂血症大鼠动脉粥样硬化指数（AI）、红细胞膜脂质以及抗氧化/促氧化状态的影响。成功制备了具有所需纳米颗粒尺寸、球形形状、高包封率（EE%）和SV持续释放特性的载SV的NLCs。生物学研究结果显示，与SV混悬液相比，给大鼠施用载SV的NLCs可提高SV的生物利用度。腹腔注射泰洛沙泊作为高脂血症诱导剂可导致血浆AI、尿酸、脂质过氧化和蛋白质氧化显著增加。同时，血浆总抗氧化能力和对氧磷酶-1活性显著降低。此外，泰洛沙泊诱导的高脂血症会增加红细胞膜胆固醇，并使红细胞抗氧化酶活性、谷胱甘肽/氧化型谷胱甘肽比值和一氧化氮水平恶化。然而，观察到红细胞促氧化活性和溶血的增加。相比之下，与接受SV混悬液的大鼠和高脂血症大鼠相比，用载SV的NLCs治疗这些大鼠可改善所测参数。载SV的NLCs的主要作用可能归因于其对SV吸收的增强、作用持续时间的延长和生物利用度的提高。因此，与SV混悬液相比，载SV的NLCs在高脂血症条件下对血脂水平和红细胞动脉粥样硬化风险显示出有利影响。
